J. CHEM. SOC. PERKIN TRANS. I 1988 2219 Photocyclisation of Enamides. Part 27.' Total Syntheses of ( + )-Yohimbine, ( +)-Alloyohimbine, and ( f )-19,20-Didehydroy~himbines~ Takeaki Naito, Yumiko Hirata, Okiko Miyata, and lchiya Ninomiya * Kobe Women's College of Pharmacy, Moto yamakita, Higashinada, Kobe 658,Japan Total syntheses of five indole alkaloids, (+)-yohimbine (lo),(+)-alloyohimbine (II), and three (amp;)-19,2O-didehydroyohimbines (I 5a, b, and c) (for the first time) were completed from a single common key intermediate (4) via a route involving the stereoselective isomerisation of the double bond of (4) followed by regioselective functionalisation of the enones (5a and b). There have been a number of investigations into the total Preparation of the Unconjugated Enone (4) and its syntheses of the biologically active yohimbines and related Stereoselective Conversion into Alloyohimbone (6a) and alkaloid^,^ most of which involve elaborate preparations of Yohimbone (6b).-Acylation of harmalane (1) with 4-methoxy- starting materials and are duly suitable for the target alkaloid.benzoyl chloride in the presence of triethylamine gave the We now report a practical and divergent synthetic route for unstable enamide (2) in quantitative yield which was various indole alkaloids including yohimbines, which takes into characterised by the n.m.r. spectrum S 4.97 and 4.40 (each 1 H, account their common skeletal structures, with total syntheses d-like, J 2 Hz) and without purification was subjected to of (+)-yohimbine, (f)-alloyohimbine, and three (amp;)-19,20- irradiation in the presence of sodium borohydride in aceto- didehydroyohimbines from a common key intermediate (4) via nitrile-methanol4 (9: 1) to afford the photocyclised lactam (3a) the route involving the stereoselective isomerisation of an homogeneously in 90 yield.The n.m.r. spectrum of the lactam unconjugated enone (4) followed by regioselective acylation of (3a)exhibited two peaks due to olefinic protons at 6 6.94 (m, 19- the resulting conjugated enones (5a and b). H) and 4.56 (s-like, 16-H), respectively, and its mass spectrum Me hlk2 (2) OMe OMe II 0 (4) HH 20 0 0 OCOzMe (5a) 20a-H (60) 20a-H (7) (5b) 20P-H (alloyohim bone) (6b) 20P-H ( yohimbone 1 (8a) R=COzMe (9) ( 10) yohimbine (11) alloyohimbine (8b) R =H Table.Isomerisation of the enone (4) in the presence of acid Acid (4) (54 (5b) L-Tartaric acid 75 L-Malic acid 75 Lactic acid 50 Mandelic acid 40 407; Succinic acid 90 conc. HCI 75 P-TsOH 60 exhibited a molecular ion peak at rn/z 320. These spectral data established the dihydrobenzene structure and the presence of an enol ether moiety in (3a). Reduction of the lactam (3a) by careful addition of an excess of lithium aluminium hydride in small portions during the course of reaction gave the corre- sponding amine (3b) in 90 yield. This was then treated with 10 hydrochloric acid in methanol at room temperature for 1 h to give the unconjugated enone (4) homogeneously in quanti- tative yield.The unconjugated enone (4) showed i.r. absorption due to a six-membered ketone at 1 720 cm-' and n.m.r. peaks due to an olefinic proton at 6 5.43 (s-like, 19-H), confirming its cyclohexenone type of structure. During purification of the unconjugated enone (4) by preparative thin layer chroma- tography (p.1.c.) on silica gel, a new spot appeared. The cis-conjugated enone (5a) was thus isolated and characterised from the following spectral evidence vmax.1 660 cm-' (C=C-CO); 6 6.89 (dt, J 10 and 1.8 Hz, 19-H) and 6.00 (dd, J 10 and 2.5 Hz, 18-H) and its structure further unambiguously established by conversion into known alloyohimbone (6a).' Thus, exclusive formation of the cis-enone (5a) from the unconjugated enone (4) in the presence of silica gel was established although the isomerisation of the 19,2O-didehydro compound (4) into the cis-18,19-didehydro compound (5a) proceeded effectively only in a small-scale experiment of below 100 mg of (4).In order to develop the practical and stereoselective transformation of the unconjugated enone (4) into either the cis-(5a) or trans-enone (Sb),we investigated the isomerisation under both acidic and basic conditions. Treatment of the unconjugated enone (4) with 10 sodium hydroxide in methanol-methylene dichloride (4:1) at 0 "C for 1 h yielded the cis-enone (5a) in 900/, yield, identical with the sample obtained above.However, under acidic conditions using various acids such as hydrochloric acid, organic mono or dibasic acids, the unconjugated enone (4) was found to isomerise to the trans-enone (5b) selectively as shown in the Table.Thus, heating the unconjugated enone (4) in dioxane at 85 OC in the presence of either tartaric acid, malic acid, or conc. hydrochloric acid gave the trans-enone (5b) in 75 yield, which showed characteristic i.r. and n.m.r. spectra v,,,, 1 680 cm-' (C=C-C=O); 6 6.80 (dd, J 10 and 1.5 Hz, 19-H) and 6.08 (dd, J 10 and 3 Hz, 18-H). The trans-enone moiety was unambiguously established by its conversion into known yohimbone (6b).5On heating in dioxane at 85 "C in the presence of conc. hydrochloric acid, the cis-enone (Sa) was isomerised into the trans-enone (5b) in 60 yield. The cis-and trans-enones (5a and b) were converted into authentic alloyohimbone (6a) and yohimbone (6b),' respec-tively, by catalytic reduction of the double bonds over platinum dioxide and 10 palladium on carbon in excellent yields.Thus, two potential key intermediates, a$-unsaturated enones (5a and b), for the synthesis of alloyohimbine and yohimbine from the common ketone (4) were stereoselectively prepared simply by selecting the reaction temperature. Total Synthesis of (+)-Yohimbine (lo), (+)-Alloyohimbine (11), and (+_)-19,20-0idehydroyohimbines(15a, b, and c) by J. CHEM. SOC. PERKIN TRANS. I 1988 Regioselective Acy1ation.-The structural features of the two enones (5a and b) having one sp3 carbon adjacent to carbonyl group at the 16-position led us to investigate the possibility of regioselective introduction of an electrophile such as a meth- oxycarbonyl group into the sterically hindered 16-position.Treatment of the trans-enone (5b) with an excess of lithium di- isopropylamide (LDA) in tetrahydrofuran at -78 OC followed by addition of methyl chloroformate gave a mixture of the acylated products which without purification was subjected to catalytic hydrogenation over platinum dioxide at room temperature under hydrogen atmosphere to afford two isolated products, the N,U-diacylated product (7) and the N,C-diacylated product (8a) in 29 and 14 yields, respectively. The former (7) showed i.r. absorption at 1 76amp;1 730 cm-' due to NC0,Me and OC0,Me and n.m.r. signals at 6 5.30 (s-like, 16- H) and 3.97 and 3.73 (each 3 H, s, OMe x 2).The structure of another product (8a) was established unambiguously from the spectral data and from its chemical conversion into authentic yohimbinone (8b) by N-deacylation with potassium carbonate in methanol.' In order to improve the yield of the 16-acylated product (8a) on acylation of the enone (5b), we next employed two alternative reaction conditions; the magnesium enolate developed by House' and the soft acylating agent provided by Mander.' House, et al.,' suggested that the magnesium enolate prepared from ketones exists in the contact ion pair structure and reacts with an acylating agent to afford preferentially the C-acylated product over the O-acylated one. Thus, treatment of the lithium enolate, prepared in situ from the trans-enone (Sb) and LDA at -78 OC, with freshly prepared anhydrous magnesium bromide followed by addition of methyl chloro- formate gave the desired 16-acylated product (9) in 68 yield with no O-acylated product.This reaction would proceed via a magnesium enolate having a contact ion pair structure which would allow an electrophile to attack exclusively at the carbon atom forming the C-acylated product (9). The desired product (9) was thus prepared regioselectively by using the magnesium enolate of the enone (5b) although the tedious preparation of anhydrous magnesium bromide was a problem. We, therefore, investigated the alternative method of the regioselective C-acylation using the soft acylating agent, methyl cyanoformate, which has been used as an excellent reagent for the preparation of the P-keto ester from a ketone by Mander, et aL9 Acylation of the lithium enolate of the trans-enone (5b) with methyl cyanoformate proceeded smoothly to give the 16-acylated product (9) in 7076 yield as the sole product.The 16-acylated product (9) corresponds to 18,19-didehydroyohimbinoneand was catalytically hydrogenated over platinum dioxide to give yohimbinone (8b) in overall 42 yield from harmalane (1) by a 7-step route. Since yohimbinone (8b) had been converted into (*)-yohimbine this synthesis completes the formal total synthesis of the parent alkaloid (i-)-yohimbine (10). Based on the result obtained in the synthesis of (-t)-yohimbine, we have also completed the total synthesis of (amp;)-alloyohimbine (11) via the same route involving regioselective acylation at the 16-position on the cis-enone (5a).Acylation of the lithium enolate, prepared in situ from the cis-enone (5a) and LDA at -78 OC, with methyl chloroformate gave a mixture of the N,C-diacylated and N,O-diacylated products (12a) and (13) in 49 and 10 yields, respectively. Acylation of either the magnesium enolate of the cis-enone (5a) with methyl chloroformate or the lithium enolate of (5a) with methyl cyanoformate gave the 16-acylated (12b) (6976 yield) or the N,C-diacylated product (12a) (90 yield), respectively. On catalytic hydrogenation over platinum dioxide, these com-pounds (12a) and (12b) gave the N-acylalloyohimbinone (14a) and alloyohimbinone (14b), respectively; the former (14a) was N-deacylated with potassium carbonate in methanol to afford alloyohimbinone (14b).The keto ester (14b) was identical with J. CHEM. SOC. PERKIN TRANS. I 1988 2221 Q OCOzMe (12a) R = C0,Me (12b) R = H (13) (l4a) R =COzMe (l4b) R = H 0 0 OH (16a) R = H (17) (16b) R = COzMe 16-H, 17-H (15a) p P 19.20-didehydroyohimbine (15b) P a 19.20-didehydro -/3 -yohimbine (15~) a j3 19,20-didehydro -a -yohimbine (1Sd) cc a unknown the authentic alloyohimbinone given by Professor Szantay.' Thus, we have succeeded in the synthesis of alloyohimbinone (14b) in overall 64 yield from harmalane (1) by an 8-step route and also in the formal total synthesis of ( f)-alloyohimbine (11) since alloyohimbinone (14b) has previously been converted into ( amp; )-alloyohimbine (11)upon sodium borohydride reduction." Finally, the applicability of our synthetic methodology using the unconjugated enone (4) as a common key intermediate was established by the accomplishment of the first total synthesis of ( +)-19,20-didehydroyohimbines (15a, b, and c) previously isolated from Aspidosperma pyricollum l1 and oblogum and characterised only by their spectral data.So far, no synthetic work of these 19,20-didehydroyohimbines except Brown's work l3 on the chemical conversion of secologanin into 19,20- didehydroyohimbinyl acetate and Martin's work 3g on the synthesis of 19,2O-didehydro-a-yohimbinehas been reported.Two 18,19-didehydro-P-keto esters (9) and (12) prepared as above would be the key intermediates for the synthesis of 19,20- didehydroyohimbines if deconjugation of the amp;unsaturated enone system would be accomplished. Thus, we investigated their deconjugation reaction and obtained the desired 19,20- didehydro-P-keto esters (16a and b) from the cis-enones (12a and b). Smooth isomerisation occurred, either by stirring a methanolic solution of the cis-enone (12b) in the presence of potassium carbonate at 0 "C or by refluxing the methanolic solution in the presence of conc. sulphuric acid, to yield the desired 19,2O-didehydro-P-keto ester (1611) in 73 or 70 yields, respectively.The structure of the 19,20-didehydro compound (16s) was established from the spectral data v,,,. 1 740, 1 680, 1 660, and 1 620 cm-' (keto and enol ester); 6 12.40 (2/3H, s, enol OH) and 5.60 (m, 19-H). Similarly, heating a methano- lic solution of the N,C-diacylated cis-enone (12a) in the presence of conc. sulphuric acid under reflux yielded the 19,20-didehydro-P-keto ester (16b) in 90 yield which was carefully treated with potassium carbonate in methanol at 15 "C to give the N-deacylated 19,20-didehydro-P-keto ester ( 16a). Treat-ment of compound (12a)with potassium carbonate in methanol at 0 "Cgave a mixture of the 19,20-didehydro compounds (16a and b) in 20 and 51 yields, respectively, the former (16a) of which would be formed as a result of N-deacylation under the basic conditions employed.On the other hand, attempted isomerisation of the trans-enone (9) to the 19,20-didehydro compound (16a) was unsuccessful even under acidic and basic conditions and the Michael adduct (17) with a methoxy group at the 19-position was obtained. Treatment of a methanolic solution of the trans-enone (9) with either potassium carbonate at 0deg;C or conc. sulphuric acid at 80deg;C gave no isomerised product (16a) but gave the methoxylated adduct (17) in 55 or 38 yield, respectively. The product (17) exhibited a molecular ion peak at m/z 382 in the mass spectrum, i.r. absorption at 1 720 cm-' due to the saturated ketone, and n.m.r. signals at 6 3.34 (s, OMe) and 3.73 (9, J 2.5 Hz, 19-H), establishing its stereostructure.The differences in the reaction course between the cis- (12a and b) and trans-enone (9) can be explained as follows. The structurally less stable cis-enones (12a and b) with a folded conformation would be readily isomerised to the thermo- dynamically more stable and planar 19,20-didehydro com- pounds (16a and b), respectively, which exist in planar conformations as shown in the Scheme. From the spectral data, the trans-enone (9) is found to exist only in a keto ester form which would act as a Michael acceptor in the presence of methanol while the cis-enones (12a and b) exist in an equilibrium mixture of the keto and enol ester, thus being less reactive as a Michael acceptor and readily isomerised to the more stable 19,20-didehydro isomers (16a and b).In the final modification of its structure, the keto ester (16a) J. CHEM. SOC. PERKIN TRANS. I 1988 H{W0H (9) A R =C02Me (12) (16) was subjected to sodium borohydride reduction at 0 "C to give a mixture of four stereoisomeric hydroxy esters (15b), (15c), (15a), and (15d) which were separated by p.1.c. on silica gel in 40, 20, 10, and 10 yields, respectively. By comparison of their n.m.r. spectra with authentic 19,20-didehydroyohimbines,the products (15b), (15c), and (15a) were identified as 19,20-di-'dehydro- P-yohimbine,' ' 19,20-didehydro-~~-yohimbine,'and 19,2O-didehydroyohimbine,' ' respectively. The fourth isomer (15d) was found to be the 17~-hydroxy-16~-methoxycarbonyl derivative from its n.m.r.spectrum which showed signals at 6 4.32 (m, 17-H) and 3.07 (t, J 4 Hz, 16-H), suggesting a methoxycarbonyl group in the 16P-axial orientation and a hydroxy group in the 17P-equatorial orientation. The application of this strategy to the synthesis of reserpine type alkaloids will be reported at a later date. Experimental 'H N.m.r. spectra were measured with JEOL PMX-60 and Varian XL-200 instruments for solutions in deuteriochloroform unless otherwise stated (tetramethylsilane as internal reference), mass spectra with JEOL JMSOlSG and Hitachi M-80 instruments, and i.r. spectra for solutions in chloroform on a Hitachi 215 spectrometer. M.p.s were determined with a Kofler- type hot-stage apparatus. The extracts from the reaction mixtures were dried over anhydrous sodium sulphate.Photochemical reactions were carried out by irradiation with a high-pressure (100 or 300 W) mercury lamp through a Pyrex filter (Eikosha, Osaka, Japan, PIH-100 or PIH-300); during irradiation, the solutions were kept at 5-10 "C whilst being stirred and treated with bubbling nitrogen. Ether refers to diethyl ether. 2,3,4,9-Tetrahydro-2-(4-methoxybenzoyl)-1 -methylene- 1 H- pyrido3,4-bindole (2).-A solution of 4-methoxybenzoyl chloride (185 mg) in anhydrous benzene (10 ml) was added dropwise to an ice-cooled, stirred solution of harmalane (1) (184 mg) and triethylamine (150 mg) in anhydrous benzene (10 ml). After being stirred at room temperature for 2 h, the solution was filtered to remove triethylamine hydrochloride.The filtrate was evaporated to give the unstable enamide (2) (3 18 mg, 99) as a pale yellow glass; 6(60 MHz) (inter ah)4.97 and 4.40 (each 1 H, d-like, J 2 Hz, C=CH,) and 3.77 (3 H, s, OMe) which was used for irradiation without further purification. 16,17,19,20- Tetradehydro- 17-methoxy-yohimban-2 1-one (3a).-Sodium borohydride (350 mg) and methanol (15 ml) were added successively to a stirred solution of the enamide (2) (31 8 mg) in acetonitrile (150 ml) at room temperature. When the added sodium borohydride had dissolved, the resulting solution was cooled to 5-10 "C and irradiated for 30 min. The reaction mixture was then evaporated at room temperature under reduced pressure.Water was added to the residue to separate the colourless solid which was recrystallised from methanol to afford the lactam (3a) (288 mg, 90), m.p. 248-250 "C; v,,,,,. 3 455 (NH), 1690 and 1655 (CX), and 1610 cm-' (NCO); 6(200 MHz) (inter ah) 7.98 (1 H, s, NH), 6.94 (1 H, m, 19-H), 5.18(1 H, m, 5-He,), 4.95 (1 H, br dd, J 12 and 4 Hz, 3-H), 4.56 (1 H, s-like, 16-H), 3.58 (3 H, s, OMe), 3.35 (1 H, m, 15-H), 3.04- 2.74 (5 H, m, 18-H,, 6-H2, and 5-Ha,), 2.56 (1 H, ddd, J 12,4, and 3.5 Hz, 14-Heq), and 1.69 (1 H, q, J 12 Hz, 14-Ha,) (Found: C, 74.3; H, 6.2; N, 8.65. C2,H,,N,O~~1/6H,O requires C, 74.3; H, 6.35; N, 8.65). 16,17,19,20- Tetradehydro- 17-methoxy-yohimban (3b).-A solution of the lactam (3a) (700 mg) in anhydrous THF (70 ml) was added dropwise to an ice-cooled, stirred solution of lithium aluminium hydride (1.0 g) in anhydrous ether (70 ml) under nitrogen.After being refluxed for 2 h, lithium aluminium hydride (700 mg) was added to the reaction mixture in small portions (several times) with nitrogen bubbling. Work-up afforded the amine (3b) (600 mg, 90), m.p. 173-1 75 "C (from methanol); v,,,. 3 480 (NH) and 1 700 and 1 660 cm-' (CX); 6(200 MHz) (inter ah) 8.84 (1 H, br s, NH), 5.59 (1 H, m, 19-H), 4.56 (1 H, br d, J 3 Hz, 16-H), 3.56 (3 H, s, OMe), 3.52 (1 H, br dd, J 12 and 2.5 Hz, 3-H), 3.44 and 3.07 (2 H, ABq, J 12 Hz, 21- H2),3.00(1H,m,15-H),2.26(1H,ddd,J12,4.5,and2.5Hz,14-He,), and 1.49 (1 H, q, J 12 Hz, 14-Ha,) (Found: C, 78.15; H, 7.4; N, 8.85.C2,H,,N,O=1/1OMeOH requires C, 77.95; H, 7.3; N, 9.05). 19,20-Didehydroyohimban-17-one (4).-10 Hydrochloric acid (18 ml) was added to a solution of the amine (3b) (250 mg) in methanol (15 ml). After being stirred at room temperature under a nitrogen stream for 1 h, the reaction mixture was evaporated. Water was added to the residue and the mixture was made alkaline by the addition of saturated aqueous sodium hydrogen carbonate, and then extracted with chloroform. The organic layer was washed, dried, and evaporated to give a solid which was triturated with ether to afford the unconjugated enone (4) (238 mg, 99); v,,,,,. 3 480 (NH) and 1720 cm-' (C==O); 6(200 MHz) (inter alia) 5.43 (1 H, s-like, 19-H), 3.54 and 3.07 (2 H, ABq, J 12.5 Hz, 21-H,), 3.40 (1 H, br d, J 12 Hz, 3-H), 2.30 (1 H, ddd, J 12, 5,and 3 Hz, 14-Heq), and 1.54 (1 H, q, J 12 Hz, 14-Ha,).This enone (4) was found to be partially isomerised to the following cis-enone (5a) as detected by t.1.c. on silica gel. (20a)-18,19-Didehydroyohimban-17-one (5a).--(a) By p.1.c. on silica gel. Purification of the crude enone (4) (76 mg) by p.1.c. (2 mm, Kieselgel60F254 Art. 5735, Merck) gave the cis-enone (5a) (68 mg, 90) as pale yellow crystals, m.p. 206-208 "C (from methanol); v,,,, 3 475 (NH) and 1 660 cm-' (CS-CO); 6(200 MHz)(interalia)7.86(1 H,s,NH),6.89(1 H,dt,JlOand 1.8Hz, 19-H), 6.00 (1 H, dd, J 10 and 2.5 Hz, 18-H), 3.25 (1 H, br d, J 11 Hz, 3-H), 1.86 (1 H, dt, J 12.5 and 5 Hz, 14-He,), and 1.72 (1 H, ddd, J 13, 12.5 and 11 Hz, 14-H,,) (Found: C, 77.9; H, 6.9;N, 9.3.Calc. for C19H,,N20: C, 78.05; H, 6.90, N, 9.6). (b) Using sodium hydroxide. A solution of 10 sodium hydroxide in methanol (60 mg) was added to an ice-cooled, stirred solution of the enone (4) (200 mg) in a mixture of methanol-methylene dichloride (4: 1) (20 ml) under a nitrogen stream. After being stirred under ice-cooling for 1 h, the reaction mixture was diluted with water and extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a solid which was recrystallised from methanol to afford the J. CHEM. SOC. PERKIN TRANS. I 1988 cis-enone (5a) (180 mg, 90) as pale yellow crystals, m.p. 206- 208 "C. This enone was identical with the cis-enone (5a) obtained by treatment with silica gel as described above.(20p)-18,19-Didehydroyohimban-17-one (5b).--(a) From the unconjugated enone (4). A solution of the unconjugated enone (4) (200 mg) and tartaric acid (100 mg) in dioxane (1 5 ml) was heated at 85 "C with stirring under a nitrogen stream for 8 h. Water was added and the mixture was extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a solid which was recrystallised from methanol to give the trans-enone (5b) (150 mg, 75) as pale yellow crystals, m.p. 224-226 "C (decomp.); v,,,. 3 500 (NH) and 1 680 cm-' (C==C-CO);m/z 292 (A#+);6(200 MHz) (inter alia) 7.80 (1 H, br s, NH), 6.80 (1 H, dd, J 10 and 1.5 Hz, 19-H), 6.08 (1 H, dd, J 10 and 3 Hz, 18-H), 3.38 (1 H, br d, J 12 Hz, 3-H), 2.12 (1 H, dt, J 12 and 3 Hz, 14-Heq), and 1.60 (1 H, q, J 12 Hz, 14-Ha,) (Found: C, 78.1; H, 6.9; N, 9.55.C19H2,N20 requires C, 78.05; H, 6.90; N, 9.6). (b) From the cis-enone (5a). Conc. hydrochloric acid (0.04 ml) was added to a solution of the cis-enone (5a) (20 mg) in dioxane (2.5 ml). After being heated at 85 "C for 8 h, the reaction mixture was diluted with water, made alkaline by the addition of saturated aqueous sodium hydrogen carbonate, and extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a solid which was recrystallised from methanol to afford the trans-enone (5b) (12 mg, 60). This enone was identical with the trans-enone (5b) by comparison of i.r.spectra and RFvalues. Isomerisation of the Unconjugated Enone (4) Under Acidic Conditions.-Following the procedure given for the isomeris- ation of the enone (4) to the trans-enone (5b) in the presence of tartaric acid, a solution of the unconjugated enone (4) (20 mg) in dioxane was warmed at 85 "C for 8 h in the presence of the respective acid. The results were collected in the Table. The products obtained were identified by comparison of the i.r. spectra and R, values with those of an authentic sample. (20a)- Yohimban- 17-one (Alloyohimbone) (6a).-A solution of the cis-enone (5a) (15 mg) in anhydrous methanol (3 ml) was catalytically hydrogenated over platinum dioxide (5 mg) under a hydrogen atmosphere at room temperature for 17 h.Work-up gave a solid which was recrystallised from methanol to afford alloyohimbone (6a) (1 5 mg, 9979, m.p. 262-265 "C (decomp.) (lit.,' 265-267 "C). This ketone was identical with the authentic alloyohimbone prepared from alloyohimbinone by a known procedure. (20p)- Yohimban- 17-one ( Yohimbone) (6b).-Following the procedure given for compound (6a), catalytic hydrogenation of the trans-enone (5b) (20 mg) over 10 palladium-carbon (5 mg) gave yohimbone (6b) (20 mg, 9973, m.p. 261-264 "C (decomp.) (from methanol) (lit.,' 263-264 "C). This ketone was identical with the authentic (+)-yohimbone prepared from (+)-yohimbine by a known pr~cedure.~,'~ Acylation of the Lithium Enolate Prepared from the trans- Enone (5b) with Methyl Chloroformate.-A solution of the trans- enone (5b) (50 mg) in anhydrous THF (5 ml) was added with stirring at -78 "C to an LDA solution, prepared from di- isopropylamine (0.12 ml) and butyl-lithium (1 5 solution in hexane) (0.38 ml) at -78 "C under a nitrogen stream.After being stirred at this temperature for 1 h, methyl chloroformate (0.07 ml) was added and the resulting solution was stirred at -78 "C for a further 1 h. After being quenched by the addition of water, the reaction mixture was extracted with methylene dichloride. The extract was dried and evaporated to give a residue which, without purification, was subjected to catalytic hydrogenation over platinum dioxide (23 mg) under a hydrogen atmosphere at room temperature for 1 h.Work-up gave a residue which was purified by p.1.c. on silica gel to afford two acylated products (7) and (8a): methyl 16,17-didehydro- 17- methoxycarbonyloxy-yohimban-1-carboxylate (7) (17.5 mg, 29) as a yellow oil, vmax. 1760-1 730 cm-I (NC0,Me and OC0,Me); 6(60 MHz) (inter alia) 7.97 (1 H, m, 12-H), 5.30 (1 H, s-like, 16-H), 4.27 (1 H, br d, J 12 Hz, 3-H), 3.97 (3 H, s, NCO,Me), and 3.73 (3 H, s, OC0,Me) (Found: M+,410.183. C,,H,,N,O, requires M, 410.184). Dimethyl (1600-17-oxoyohimban- 1,16-dicarboxylate (8a) (8.4 mg, 14), m.p. 166- 169 "C) (from ether-methanol); v,,,. 1 740 (NC0,Me and CC0,Me) and 1720 cm-l (CO); 6(60 MHz) (inter aka) 8.13 (1 H,m,12-H),4.00(3 H,s,NCO,Me),and 3.77(3 H,s,CCO,Me) (Found: M+,410.183. C,,H,,N,O, requires M, 410.184).Methyl (16a)-17-0xoyohimban-16-carboxy1ate (Yohimbin-one) (8b).-A mixture of the N,C-diacylated product (8a) (8.4 mg), potassium carbonate (15 mg), and methanol (5 ml) was stirred under a nitrogen stream at room temperature for 3 h. After being diluted with water, the reaction mixture was extracted with methylene dichloride, then washed, dried, and evaporated to give a solid which was recrystallised from methanol to afford yohimbinone (8b) (7 mg, 97), m.p. 226- 227 "C (decomp.) (lit.,, 239deg;C); vmax. 3 500 (NH), 1 745 (CO,Me), and 1720 cm-' (CO); m/z 352 (M'); G(CDC1,-CD,OD) (200 MHz) (inter alia) 3.84 (3 H, s, CO,Me), 3.28 (1 H, d, J 12 Hz, 16-H), 3.29 (1 H, br d, J 11 Hz, 3-H), and 1.42 (1 H, q, J 11 Hz, 14-H,,) (Found: C, 70.65; H, 6.85; N, 7.95.Calc. for C,,H,,N,O3~1/4H2O: C, 70.65; H, 6.9; N, 7.85). This ketone (8b) was identical with authentic yohimbinone, provided by Professor Szantay,, by comparison with their i.r. and n.m.r. spectra and RF values and mixed m.p. Acylation of the Magnesium Enolate of the trans-Enone (5b) with Methyl Chloroformate.-A solution of freshly prepared anhydrous magnesium bromide (35 mg) was added to a solution of the lithium enolate, prepared from the trans-enone (5b) (50 mg), di-isoproylamine (0.05 ml), and butyl-lithium (15 solution in hexane) (0.16 ml) according to the procedure described above, with stirring under a nitrogen stream at -78 "C. After being stirred at -78 "C for 40 min, methyl chloroformate (0.029 ml) was added and the reaction mixture was stirred under a nitrogen stream at -78 "C for 1 h.Water was then added and the reaction mixture was extracted with methylene dichloride. The extract was dried and evaporated to give a residue which was purified by p.1.c. on silica gel to afford methyl (1 6a)- 18,19-didehydro- 17-oxoyohimban- 1 6-carb- oxylate (9) (41 mg, 68) as pale yellow crystals, m.p. 216- 218 "C (from methanol); vmax. 3 495 (NH), 1740 (CO,Me), 1680 (C=C-CO), and 1620 cm-I (W);G(200 MHz) (inter alia) 7.88 (1 H, br s, NH), 6.82 (1 H, dd, J 10 and 2 Hz, 19-H), 612(1H,dd,JlOand3Hz, l8-H),3.89(3H,s,CO2Me),3.41(1 H, br d, J 12 Hz, 3-H), 2.13 (1 H, dt, J 12 and 3 Hz, 14-Heq), and 1.56 (1 H, q, J 12 Hz, 14-Ha,) (Found: C, 71.95; H, 6.45; N, 7.85.C,,H,,N,O, requires C, 72.0; H, 6.35; N, 8.0). Acylation of the Lithium Enolate of the trans-Enone (5b) with Methyl Cyanoformate.-Acylation of the lithium enolate, prepared from the trans-enone (5b) (50 mg) and LDA, with methyl cyanoformate (32 mg), and purification of the crude product by p.1.c. on silica gel afforded the ester (9) (42 mg, 70) which was identical with the sample obtained above. Catalytic Hydrogenation of the C-Acylated Compound (9).-A solution of the ester (9) (30 mg) in anhydrous methanol (10 ml) was subjected to catalytic hydrogenation over platinum dioxide (10 mg) under a hydrogen atmosphere at room temperature for 1 h. Work-up gave a solid which was recrystal- lised from methanol to afford yohimbinone (8b) (30 mg, 99).This ester (8b) was identical with the sample prepared by N-deacylation of (8a) prepared above. Acylation of the cis-Enone @a).-(a) By acylation of the lithium enolate with methyl chloroformate. Following the procedure given for (5b), acylation of the lithium enolate of the cis-enone (5a) (50 mg) with methyl chloroformate (0.029 ml) followed by purification of the crude product by p.1.c. on silica gel afforded the N,C-diacylated product (12a) (34 mg, 49) and the N,O-diacylated product (13) (7 mg, 10); dimethyl (20a)- 18,19-didehydro-17-oxoyohimban-l,l6-dicurboxylute(12a) as a yellow oil, vmax. 1 735, 1680, 1660, 1620, and 1590 cm-' (NC0,Me and C=CCOCHCO,Me); 6(200 MHz) (inter alia) 11.94 (3/5 H, br s, enolic OH), 6.95 (2/5 H, dt, J 10 and 2 Hz, 19- H of keto form), 6.34 (3/5 H, dt, J 10 and 2 Hz, 19-H of enol form), 6.07 (2/5 H, dd, J 10 and 2.5 Hz, 18-H of keto form), 5.99 (3/5 H, dd, J 10 and 3 Hz, 18-H of enol form), 4.08 (6/5 H, NC0,Me of keto form), 4.04 (9/5 H, s, NC0,Me of enol form), 3.86 (9/5 H, s, CC0,Me of enol form), 3.76 (6/5 H, s, CCO,Me, of keto form), 2.10 (2/5 H, br d, J 11 Hz, 14-Heq of keto form), 2.03 (3/5 H, ddd J 11,4, and 2 Hz, 14-He, of enol form), 1.68 (2/5 H, td, J 12 and 11 Hz, 14-Ha, of keto form), and 1.47 (3/5 H, td, J 12 and 11 Hz, 14-Ha, of enol form) (Found: M', 408.169.C2,H,,N,05 requires M, 408.168). Methyl (20a)-16,17,18,19- tetradehydro-17-methoxycarbonyloxy-yohimban-1 -carboxylate (13) as a yellow oil, vmax,1760-1 730 cm-' (NC0,Me and OC0,Me); 6(60 MHz) (inter alia) 7.90 (1 H, m, 12-H), 5.78 (2 H, br s, 18- and 19-H), 5.50 (1 H, br d, J4 Hz, 16-H), 4.00 (3 H, s, NCO,Me), and 3.77 (3 H, s, OC0,Me) (Found: M+,408.171.C23H24N205requires M, 408.168). (b) By acylation of the magnesium enolate with methyl chloroformate. According to the procedure given for (5b), acylation of the magnesium enolate of the cis-enone (5a) (50 mg) with methyl chloroformate followed by purification of the crude product by p.1.c. on silica gel afforded methyl (20a)-18,19- didehydro-17-0xoyohimban-16-carboxylate(12b) (41.5 mg, 69) as a pale yellow oil, v,,,. 3 490 (NH), 1 735, 1 680, 1 655, 1 620, and 1585 cm-I (C=CCOCHCO,Me); 6(200 MHz) (inter alia) 11.98 (1/2 H, br s, enolic OH), 8.10 and 7.83 (each 1/2 H, br s, NH), 6.93 (1/2 H, dt, J 10.5 and 2 Hz, 19-H of keto form), 6.36 (1/2 H, dt, J 10 and 1.5 Hz, 19-H ofenol form), 6.07 (1/2 H, dd, J 10.5and 3 Hz, 18-H of keto form), 6.00 (1/2 H, dd, J 10 and 3 Hz, 18-H of enol form), 3.87 and 3.74 (each 3/2 H, s, CO,Me), 3.30 and 3.16 (each 1/2 H, br d, J 12 Hz, 3-H), 1.96 (1/2 H, dt, J 12 and 3 Hz, 14-Heq), 1.90 (1/2 H, dt J 12 and 4 Hz, 14-Heq), and 1.71 and 1.57 (each 1/2 H, q, J 12 Hz, 14-Ha, (Found: M+, 350.163.C,,H,,N,O, requires M, 350.163). (c) By acylation of the lithium enolate with methyl cyano- formate. Following the procedure given for (5b), acylation of the lithium enolate of the cis-enone (5a) (100 mg) with methyl cyanoformate (62 mg) followed by purification by p.1.c.on silica gel afforded the N,C-diacylated product (12a) (126 mg, 90) identical with the sample (12a) obtained in (a). Methyl (20a)- 17-Oxoyohimban- 16-carboxylate (Allo-yohimbinone) (14b).-Following the procedure given for (9), catalytic hydrogenation of the C-acylated product (12b) fol- lowed by purification by p.1.c. on silica gel afforded the keto ester (14b) (30 mg, 97) as a yellow oil which was identical with the authentic alloyohimbinone (14b) provided by Professor Szantay lo by comparison of their i.r. and n.m.r. spectra and R, values; vmax. 3 490 (NH), 1750, 1720, 1660, and 1620 cm-' (COCHC0,Me); 6(200 MHz) (inter alia) 12.37 (4/7 H, s, enolic OH), 7.80 (1 H, br s, NH), 3.87 (3 H, s, CO,Me), 3.28 (1 H, br d, J 12 Hz, 3-H), and 1.53 (1 H, q, J 12 Hz, 14-Ha,) (Found: M+, 352.180.Calc. for C,,H,,N,O,: M, 352.179). J. CHEM. SOC. PERKIN TRANS. I 1988 Dimethyl (20a)- 17-Oxoyohimban- 1,16-dicarboxylate (14a).- Following the procedure given for (9),catalytic hydrogenation of (12a) (30 mg) followed by purification by p.1.c. on silica gel afforded the keto ester (14a) (29.5 mg, 98) as a yellow oil, vmax. 1740-1 720, 1655, and 1610 cm-' (NC0,Me and COCHC0,Me); 6(200 MHz) (inter alia) 12.33 (4/3 H, s, enolic OH), 8.07 (1 H, dd, J8 and 2 Hz, 12-H),4.03 (3 H, s, NCO,Me), 3.83 (3 H, s, CCO,Me), 3.72 (1 H, br d, J 10.5 Hz, 3-H), 2.38 (1 H, br d, J 12 Hz, 14-Heq), and 1.30(1 H, td, J 12 and 10.5 Hz, 14- Hax) (Found: M+,410.183. C2,H,,N,0, requires M, 410.184).N-Deacylation of the N,C-Diacylated Compound (14a).- According to the procedure given for (8a), treatment of the N,C-diacylate (14a) (20 mg) with potassium carbonate in methanol gave the keto ester (14b) (17 mg, 9973, identical with authentic alloyohimbinone prepared by catalytic hydrogenation of (12b). Methyl 19,20-Didehydro- 17-oxoyohimban- 16-carboxylate (16a).-(a) Using potassium carbonate. A mixture of the keto ester (12b) (25 mg), potassium carbonate (25 mg), and methanol (4 ml) was stirred at 0 "C under a nitrogen stream for 2 h. Water was then added and the mixture was extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a residue which was purified by p.1.c. on silica gel to afford the unconjugated enone (16a) (18.3 mg, 73) as a yellow oil, v,,,.3 500 (NH), 1 740, 1 680, 1 660, and 1 620 cm-' (COCH- C0,Me and CS); 6(200 MHz) (inter ulia) 12.40 (2/3 H, s, enolicOH),7.80(1 H, brs,NH), 5.60(1 H,m, 19-H),3.94(2H,s, C0,Me of enol form), 3.90 (1 H, s, C02Me of keto form), 3.64 (1 H, br d, J 12 Hz, 3-H), 3.51 and 3.41 (2 H, ABq, J 11 Hz, 21- H2),2.68 (1 H, dt, J 12 and 3 Hz, 14-Heq), and 1.43 (1 H, q, J 12 Hz, 14-Ha,) (Found: M+, 350.164. C,,H,,N,O, requires M, 350.163). (b) Using conc. sulphuric acid. A solution of the keto ester (12b) (10 mg) and conc. sulphuric acid (40 mg) in methanol (5 ml) was refluxed under a nitrogen stream for 7 h. During the course of reaction, conc. sulphuric acid (ca. 40 mg) was added to the mixture; the reaction rate was checked by t.1.c.on silica gel. After being cooled, the reaction mixture was diluted with water, made alkaline by the addition of saturated aqueous sodium hydrogen carbonate, and extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a residue which was purified by p.1.c. on silica gel to afford the 19,20-didehydro compound (16a) (7 mg, 70), identical with the sample obtained in (a). Dimethyl 19,20- Didehydro- 17-oxoyohimban- 1,16-dicarboxyl- ate (16b).-Following the procedure given for (12b), treatment of the 18,19-didehydro compound (12a) (50 mg) with conc. sulphuric acid followed by purification by p.1.c. on silica gel afforded the 19,20-didehydro compound (16b) (45 mg, 90) as a yellow oil, v,,,.1 730,l 655, and 1 620 cm-' (NCO,Me, C=C, and COCHC0,Me); 6(200 MHz) (inter alia) 12.36 (1 H, s, enolic OH), 8.08 (1 H, dd, J8 and 2 Hz, 12-H), 5.49 (1 H, br s, 19-H), 4.67 (1 H, br d, J 12 Hz, 3-H), 4.09 (3 H, s, NCO,Me), 3.86 (3 H, s, CCO,Me), 3.74 (1 H, br d, J 13 Hz, 21-Heq), 3.38 (1 H, d, J 13 Hz, 21-Ha,), 3.38 (1 H, m, 15-H), 2.69 (1 H, ddd, J 12,4, and 3 Hz, 14-Heq), and 1.45 (1 H, q, J 12 Hz, 14-Ha,) (Found: M+, 408.167. C,3H,,N,0, requires M, 408.168). Isomerisation of the N-Acyl- 18,19-didehydro Compound (12a) with Potassium Carbonate.-Following the procedure given for (12b), treatment of the N-acylate (12a) (35 mg) with potassium carbonate followed by p.1.c. on silica gel gave the N-acyl-l9,20- didehydro compound (16b) (18 mg, 51) and the 19,20-didehydro compound (16a) (6 mg, 20) which were identical with the respective samples (16b) and (16a) obtained by iso- merisation of the 18,19-didehydro compounds (12a) and (12b).J. CHEM. SOC. PERKIN TRANS. I 1988 N-Deacylation of the N-Acyl-19,20-didehydro Compound (16b).-A mixture of the N-acyl- 19,20-didehydro compound (16b) (20 mg), potassium carbonate (20 mg), and methanol (3 ml) was stirred at 15 "C for 5 h. The reaction mixture was diluted with water and extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a residue which was purified by p.1.c. on silica gel to afford the 19,20- didehydro compound (16a) (3 mg, 17) and the starting material (16b) (5 mg).The 19,20-didehydro compound (16a) was identical with the sample obtained by isomerisation of (12b). Methyl (16a,19a)- 19-Methoxy- 17-oxoyohimban-16-carboxyl-ate (17).-Following the procedure given for (12b), treatment of the keto ester (9)(between 10 and 12 mg) with either potassium carbonate or conc. sulphuric acid in methanol followed by purification by p.1.c. on silica gel afforded the identical 19-methoxy adduct (17) (6 mg, 55 with potassium carbonate) or (5 mg, 389.; with conc. sulphuric acid), m.p. 165-167 "C (from methanol); v,,,, 3 490 (NH), 1 740 (CO,Me), and 1 720 cm-' (C=O);6(200 MHz) (inter ah) 7.92 (1 H, br s, NH), 3.86 (3 H, s, CO,Me), 3.73 (1 H, q, J2.5 Hz, 19-H), 3.36 (1 H, br d, J 12.5 Hz, 3-H), 3.34 (3 H, s, OMe), 2.94 (1 H, dd, J 13.5 and 2.5 Hz, 18- He,), 2.43 (1 H, dd, J 13.5 and 2.5 Hz, 18-Ha,), 2.20 (1 H, dt, J 12.5and 3.5 Hz, 14-He,), 2.12 (1 H, tdd, J 11,4, and 2.5 Hz, 20- H), and 1.44 (1 H, q, J 12.5 Hz, 14-Ha,) (Found: M+, 382.187.C2,H2,Nz0, requires M, 382.189). Reductiorr of the 19,20-Didehydro Compound (16a) with Sodium Borohydride.-A solution of the 19,20-didehydro compound (16a) (20 mg) and sodium borohydride (15 mg) in methanol (5 ml) was stirred at 0 "C for 30 min. Water was added to the reaction mixture and the mixture was extracted with methylene dichloride. The extract was washed, dried, and evaporated to give a residue which was purified by p.1.c. on alumina to afford a mixture of four stereoisomeric hydroxy esters which were separated; methyl 19,2O-didehydro- 17- hydroxy-jwhimban- 16-carboxylates (15b) (8 mg, 40), (1) (4 mg, 20"/,,), (15a) (2 mg, lo), and (19) (2 mg, 10) all as yellow oils.The hydroxy esters (15b) and (1) were identical with 19,20-didehydro-~-yohimbineand 19,20-didehydro-a-yohim-bine, respectively, both of which were provided by Professor Potier l2 by comparisons of the i.r. and n.m.r. spectra. 1.r. and n.m.r. spectral data of the third hydroxy ester (15a) were consistent with those of 19,20-didehydroyohimbine reported by Professor Djerassi.' ' Compound (15b), v,,,. 3 600 (OH), 3 500 (NH), and 1 720 cm-' (C0,Me); 6(200 MHz) (inter alia) 7.82 (1 H, br s, NH), 5.56 (1 H, br d, J5.5 Hz, 19-H), 4.08 (1 H, td, J 10.5 and 5.5 Hz, 17-H), 3.86 (3 H, s, CO,Me), 3.44 (1 H, d, J 12 352.178).Compound (15a), vmax.3 500 (NH) and 1 730 cm-' (C0,Me); 6(200 MHz) (inter ah) 7.80 (1 H, br s, NH), 5.58 (1 H, br s, 19-H), 4.37 (1 H, br s, 17-H), 3.84 (3 H, s, CO,Me), 3.51 (1 H, br d, J 12 Hz, 3-H), 3.46 (1 H, d, J 12.5 Hz, 21-He,), 2.48 (1 H, dd, J 10.5 and 1.5 Hz, 16-H), 2.36 (3 H, m, 14-He, and 18-H2), and 1.41 (1 H, q, J 12 Hz, 14-Ha,) (Found: M+, 352.180). Compound (lg), v,,,, 3 500 (NH) and 1 720 cm-' (C0,Me); 6(200 MHz) (inter ah) 7.76 (1 H, br s, NH), 5.74 (1 H, br d, J 5 Hz, 19-H), 4.32 (1 H, m, 17-H), 3.76 (3 H, s, C02Me), 3.30 (1 H, br d, J 12 Hz, 3-H), 3.07 (1 H, t, J4 Hz, 16-H), 2.00 (1 H, dt, J 12 and 3.5 Hz, 14-Heq), and 1.78 (1 H, q, J 12 Hz, 14-Ha,) (Found: M', 352.180).Acknowledgements The authors thank the Ministry of Education, Science, and Culture (Japan) for a research grant and Professor Cs. Szantay for a gift of yohimbinone and alloyohimbinone and Dr. P. Potier for gifts of spectral data of 19,20-didehydroyohimbines and their generous encouragement. References 1 Part 26, T. Naito, 0.Miyata, Y. Tada. Y. Nishiguchi, T. Kiguchi, and I. Ninomiya, Chem. Pharm. Bull., 1986, 34, 4144. 2 Preliminary communications, 0.Miyata, Y. Hirata, T. Naito, and I. Ninomiya, J.Chem. SOC.,Chem. Commun., 1983,123 1; 0.Miyata, Y. Hirata, T. Naito, and 1. Ninomiya, Heterocycles, 1984, 22, 2719. 3 (a) H. J. Monteiro, 'The Alkaloids,' ed. R. H. F. Manske, Academic Press, New York, 1968, vol.XI, p. 145; (b) R. T. Brown, 'The Chemistry of Heterocyclic Compounds,' (Indoles, Part 4, ed. J. E. Saxton), eds. A. Weissberger and E. C. Taylor, John Wiley and Sons, Inc., New York, 1983, vol. 25, p. 147; (c)Cs. Szantay, G. Blasko, K. Honty, and G. Dornyei, 'The Alkaloids,' ed. A. Brossi, Academic Press, New York, 1986, vol. 27, p, 131; (d)M. Isobe, N. Fukami, and T. Goto, Chem. Lett., 1985, 71; (e) R. Riva, L. Banfi, B. Danieli, G. Guanti, G. Lesma, and G. Palmisano, J. Chem. SOC.,Chem. Commun., 1987, 299; (f)S. A. Godleski and E. B. Villhaner, J. Org. Chem., 1986, 51, 486; (g) S. F. Martin and H. Riieger, Tetrahedron Lett., 1985, 26, 5227. 4 T. Naito, Y. Tada, Y. Nishiguchi, and I. Ninomiya, J. Chem. Soc., Perkin Trans. I, 1985, 487. 5 Cs. Szantay, K. Honty, L. Toke, and L. Szabo, Chem. Ber., 1976,109, 1737. 6 L. Toke, K. Honty, and Cs. Szantay, Chem. Ber., 1969, 102, 3248. 7 M. Ikeda, S. Matsugashita, and Y. Tamura, J. Chem. SOC., Perkin Trans. I, 1976, 2587. 8 H. 0.House, R. A. Auerbach, M. Gall, and N. P. Peet, J.Org. Chem., 1973, 38, 514. 9 L. N. Mander and S. P. Sethi, Tetrahedron Lett., 1983, 24, 5425. 10 L. Toke, Z. Gombos, G. Blasko, K. Honty, L. Szabo, J. Tamas, and Cs. Szantay, J. Org. Chem., 1973, 38, 2501. Hz,21-He,),3.38(1H,brd,J12Hz,3-H),2.44(1H,t,J10.5Hz,11 R. R. Arndt and C. Djerassi, Experientiu, 1965, 21, 566. 12 G. M. T. Robert, A. Ahond, C. Poupat, P. Potier, H. Jacquemin, and 16-H),2.24(1H,ddd,J12,5,and3Hz,14-Heq),2.14(1H,m,18-Ha,), and 1.46 (1 H, q, J 12 Hz, 14-H,,) (Found: M', 352.179. S. K. Kan, J. Nat. Prod., 1983, 46, 708. Calc. for C,,H,,N,O,: M, 352.179). Compound (15c), v,,,. 13 R. T. Brown and S. B. Pratt, J.Chem. Soc., Chem. Commun., 1980,165. 3 500 (NH) and 1 720 cm-' (C0,Me); 6(200 MHz) (inter alia) 14 J. D. Albright and C. Goldman, J. Org. Chem., 1965, 30,1107. 7.80(1H,brs,NH),5.60(1H,brs,19-H),4.31(1H,td,J5and3 Hz, 17-H), 3.78 (3 H, s, CO,Me), 3.46 (1 H, d, J 12 Hz, 21-He,), 3.46 (1 H, br d, J 12 Hz, 3-H), 3.00 (1 H, dd, J7 and 3 Hz, 16-H), 2.36 (2 H, m, 18-H2), and 1.94 (2 H, m, 14-H2) (Found: M+, Received 5th October 1987; Paper 711770
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