1974 909Addition of Dichlorocarbene to Steroidal Olefins. Preparation of aStereoisomer of Demethylgorgosterol, a Cyclopropane-containingMarine SterolBy Younus M. Sheikh, Jacques Leclercq, and Carl Djerassi,' Department of Chemistry, Stanford University,Stanford, California 94305, U.S.A.Dichlorocarbene generated by pyrolysis of sodium trichloroacetate added to the 24.28-double bond of 5u-stigmast-24(28)-ene A24(28)-fucostene (6) but failed to add to either the 5.6- or 22.23-double bond of ergosta-5.22-dien-3p-01 (brassicasterol) (1 9). However, dichlorocarbene generated by reaction of sodium hydroxide with chloroformin the presence of benzyltriethylammonium bromide added from the p side to the 5.6-double bond of cholesteryl (9),stigmasteryl (1 2). and brassicasteryl (1 8) acetates, to the 7,8-double bond (from the u side) of cholest-7-en-3P-yl(1 0) and 5a-ergosta-7,22-dien-3p-yI (1 7) acetates, and to the 22,23-double bond of 5u-ergost-22-en-GP-yl (1 1 )and brassicasteryl (1 8) acetates.IN connection with our work on steroids and terpenoidsfrom marine sources and in view of the biogeneticsignificance of the unusual cyclopropane-containingmarine sterols gorgosterol 1,2 (1), demethylgorgosterol(2), acanthasterol (3), and 9-oxo-9,l l-secogorgost-5-ene-3p,ll-dio15 (4), we have been engaged in syn-thetic studies of such sterols for some years.SinceX-ray diffraction analysis 295 of (l), (2), and (4) hadalready established the presence of a transoid cyclo-R. L. Hale, J. Leclercq, B. Tursch, C.Djerassi, R. A. Gross,jun., A. J. Weinheimer, K. Gupta, and P. J. Scheuer, J . Amer.Chem. SOC., 1970, 92, 2179.N. C. Ling, R. L. Hale, and C . Djerassi, J . Amer. Chem. Soc.,1970, 02, 5281.a F. J. Schmitz and T. Pattabhiraman, J . Amer. Chem. Soc.,1970, 92, 6073.propane ring (the configuration at carbon atoms 22,23, and 24 is R), we decided to employ the side chainof AB-olefinic steroids and introduce the additionalmethyl and methylene groups after appropriate pro-tection of the As-3P-hydroxy-system. The recentreport by Ikan et prompts us to report our resultssince these differ somewhat from those of the Israeliauthors.* K. C. Gupta and P. J. Scheuer. Tetrahedron, 1967, 24, 6831;Y. M. Sheikh, C . Djerassi, andB. M. Tursch, Chem.Comm., 1971,217, 600.5 E. L. Enwell, D. V. Der Helm, I. H. Hsu, T. Pattabhiraman,F. J. Schmitz, R. L. Spraggins, and A. J. Weinheimer, J.C.S.Chem. Comm., 1972. 216.6 R. Ikan, A. Markus, and 2. Goldschmidt, J.C.S. Perkin I ,1972, 2423910 J.C.S. Perkin ICarbenoid addition to a trans A22-steroidal doublebond appeared attractive. Although both stereo-isomers were expected, it was hoped that a suitableseparation procedure could be worked out, However,our limited attempts to methylenate the 22,23-doublebond of brassicasterol (19) under a variety of Simmons-Smith ' conditions with or without protection of theAs-3P-hydroxy-system as a 3,5-cyclo-6-ether * or 6-ace-tate resulted in recovery of starting material.HO(1) R = Me, As, (22R,23R,24R)(2) R = H, As, (22R,23R,24R)(3) R = Me, A', 5a(22R,23R,24R)that benzyltriethylammonium bromide is a truemicelle,12 and that the carbenoid addition takes placeat the interface, then it is expected that the more polargroup (acetate in the present case) will be orientedtowards the charge heads while the steroidal side chainshould be hidden in the lipophilic portion of the micelle.Since the frequency of exposure to carbenoid additionof various double bonds should decrease with increasingdistance from the charge heads, the addition shouldHO(4) (22R,23R2,24R)M P(6) R1 = Ac, R2 = CH:CHCH(Me)*CHMe,(R)(6)Methylene addition to A24(28)-fucostene (6) viaSimmons-Smith reaction proceeded in poor yield(10) but dichlorocarbene generated by pyrolysis ofsodium trichloroacetate qlo added readily (69 yield)to furnish the dichloro-adduct (7) which on subsequentdechlorination with lithium in ammonium gave thehydrocarbon (8).However, dichlorocarbene generatedby the foregoing method did not add to the 22,23-double bond of brassicasterol (19).As an alternative source of a more reactive dichloro-carbene, we examined a procedure recently developedby Dehmlow et aZ.ll Assuming that 5,6- and 22,23-steroidal double bonds are equally sterically accessible ,a) 24,25-Methylenelanost-8-en-3~-ol has recently beenprepared, C. R. Toubiana and E. Lederer, Bull. SOC. chim. France,1963, 2663, by Simmons-Smith reaction; (b) R. D. Smith andH. E. Simmons, Org. Synth., 1961, 41, 72; R. Ginsig and A.DCross, J . Amer. Chem. SOC., 1965, 87, 4629; R. J. Rawson andI. T. Harrison, J . Org. Chem., 1970, 35, 2057.E. Fernholz and W. L. Ruigh, J . Amer. Chem. Soc., 1940,62, 3346; J. A. Steele and E. Mosettig, J . Org. Chem., 1963, 28,671.S. W. Toby and R. West, Tetrahedron Letters. 1963, 1179;S . W. Toby and R. West, J . Amer. Chem. Soc., 1966, 88, 2481;W. R. Moore, S. E. Krikorian, and J . E. La Prade, J . Org. Chem.,1963, 28, 1404.lo In our experiment dichlorocarbene generated by phenyl-(trihalogenomethyljmercury (W. E. Parham and R. J. Sperley.J . Org. Chem., 1967, 32, 926) failed t o add to brassicasterol (19).T. Powers, unpublished results.;r(7) K = C1(8) R = Htake place preferentially at the nuclear unsaturationin the presence of the 22,23-double bond in steroids withnuclear and side chain unsaturations.Indeed, di-chlorocarbene generated by the foregoing procedurereadily added to cholesteryl acetate (9) from the P-sideto furnish the adduct (20) and to cholest-7-en-3p-ylacetate (10) from the a-side to provide the adduct (28).These observations are apparently different from theprevious observations 1 3 9 1 4 wherein both dichloro- anddibromo-carbenes were inert l5 to A6-steroids bearing alop-methyl group although a attack did occur with a5,7-diene13 and p attack with a 3,5-diene.14 Thestructure and stereochemistry of our adducts (20) and(28) was established by sodium-ammonia dechlorinationl1 M. Makosza and W. Wawryniewicz, Tetrahedron Letters,1969, 4669; E.V. Dehmlow and J. Schonfeld, Annalen, 1971,744, 42; E. V. Dehmlow, Tetrahedron, 1971, 27, 4071; 1972, 28,176; G. C. Joshi, N. Singh, and L. M. Pande, Tetrahedron Letters,1972, 1461.le E. H. Cordes and C. Gitler, ' Reaction Kinetics in thePresence of Micelle-forming Surfactants,' in ' Progress in Bio-Organic chemistry,' vol. 1, eds. E. J. Kaiser and F. J. Kezdy,Wiley-Interscience, New York, 1973, pp. 1-53.l3 M. 2. Nazer, J . Org. Chem., 1965, 30, 1737.l4 L. H. Knox, E. Velarde, S. Berger, D. Guadriello, P. W.Landis, and A. D. Cross, J . Amer. Chem. SOC., 1963, 85, 1851.l 5 Dichlorocarbene prepared by pyrolysis of PhHgCC1, hasrecently been added to the more nucleophilic 6-methylcholest-5-en-3P-yl benzoate (F. T. Bond and R. H.Cornelia, Chem. Comm.,1968, 1189)1974 911to the cyclopropane steroids (21) l6 and (29) and their sodium-ammonia reduction furnished (25). Its masssubsequent Jones oxidation to the corresponding spectrum had peaks at m/e 287 and 285 correspondingketones (23) 16 and (30), which displayed the expected l6 to loss of the side chain with or without transfer of twoCotton effects. hydrogens l7 and at m/e 245 representing the typicalR3R 39.) I R3"- R 2 H/ORc / OAC /OAC/OH /OAc /OH(9) R' = .~ , R2 = R3 =z H, A5 (20) R' = ,. , R2 = Cl,R3 = H (28) R' = .,, , RZ = C1,R3 =- H".H 'II H '* H(29) R' = .~ , R2 = R3 = H (10) R' = I , R2 = H2,R3 = H,A7,5a (21) R1 = . , Re = R3 = Hbsol;. H ''bsol; H ' ' s H/OAc /OAC (30) R' = 0, R2 = R3 =1 H(31) R' = .. , R? = C:l,R3 = P-Me,A22/0.4c (11) R' = H,, R2 = . , R3 = P-Me,A2, (22) R1 = .., R2 = R3 = H '.. H '.H/ORc (23) R' = 0, R2 = R3 = H ... H/OAc /OAc',. H '* H(14) R' = 0, R2 = H,,R3 = a-Et,A',A22 ".H '.H(12) R' = ., , R2 1 H,R3 = a-Et,A6,A22".H(24) R' = .. , R2 = Cl,R3 = u-Et,A22 (32) R' = ..L , R2 = H,R3 = @-Me,A22, R2 = H,R3 = a-Et,A22 (33) K1 = (OH, R2 = H,R3 = P-Me,A22/OH/OH (13) R' = -... , R2 = H,R3 = a-Et,A6,A22(25) R1 = .. *H(15) R' = 0, R2 = H2,R3 = cr-Et,4-Me,A4,A22 (26) R1 = 0, R2 = H,R3 = a-Et,A?e(16) R' = R2 = H,,R3 = a-Et,Az2 /OH(17) R' = .. , R2 = H2,R3 = P-Me,A7,AZ2(34) R1 = 0, R2 = H,R3 = P-Me,A22(27) R' = , R2 = H,R3 = @-Me,A22/OAc ". H".H/OAc".H(18) R' = ,, , R2 = H,R3 = P-Me,A6,A22(19) R' = (OH, R2 = H,R3 = P-Me,A6,A22*HContrary to the behaviour with A5- and A'-sterols,dichlorocarbene addition to 5a-ergost-22-en-6P-yl ace-tate (11) proceeded slowly and resulted in a complexmixture which on subsequent dechlorination andpreparative g.1.c.furnished one pure compound (lo)which was assigned tentatively structure (35) on thebasis of its retention time and mass spectrum.Dichlorocarbene addition to stiginasteryl acetate (12)provided only one adduct (24) which on subsequentL. Kohout and J. Fajkos, CoZZ. Czech. Chem. Comm., 1972,3490.l7 S. G. Wyllie and C. Djerassi, J. Org. Chenz., 1968, 33, 305.ring D 18 cleavage of steroids. The mass spectrumof (25) in conjunction with its n.m.r. spectrum indicat-ing the presence of only three cyclopropane protons(6 -0.03 to 0.65) and two olefinic protons (6 5.06)and the C-19 methyl signal l6 at 6 0-90 firmly establishedthe structure and stereochemistry of (25).Jonesoxidation of (25) led to the ketone (26) which displayedno U.V. absorption in the 240 nm region in both basicand neutral medium and gave a positive Cottoii effect l 6as expected.The mass spectra of (25) and (26) also contained peaksat mle 314 and 312, respectively, corresponding tocleavage of the C-20-C-23 bond with concomitanttransfer of one hydrogen and do not represent formalcleavage of a cyclopropane l9 between positions 22 and23. Apparently this C-20-C-22 bond fission is a commonfeature of steroids e.g. m/e 300 in (13) of the stigmastane18 L. Tokes, G.Jones, and C. Djerassi, J. Amev. Chem. SOC.,1968, 90, 5465.l9 J. R. Dias and C. Djerassi, Org. Muss Spectrometry, 1973, 7,753912 J.C.S. Perkin Iseries carrying 20,22-unsaturation, e.g. (13) m/e 314(5) and 300 (17), (14) m/e 312 (8) and 298 (34),(15) m/e 326 (20) and 312 (54), and (16) m/e 300 (6) and286 (42). The peaks at m/e 314, 312, 326, and 300 incompounds (13), (14), (15), and (16) respectively possiblyare generated by movement of the 22,23-double bondafter ionization to C-23 followed by cleavage of theC-22-C-23 bond with transfer of one hydrogen.A similar reaction sequence with 5a-ergosta-7,22-dien-3p-yl acetate (17) furnished compounds (31)-(34)whose structures were consistent with their spectralCH4 spectrometers operating at 70 eV using a direct inletsystem.High resolution measurements were obtainedwith the MS9 instrument on line to the ACME computerfacility of the Stanford University Medical Centre.Ofipenauer Oxidation of Fucosterol.-A mixture offucosterol (2 g) in dry toluene (100 ml), distilled cyclo-hexanone (20 ml), and aluminium isopropoxide (2.5 g)was refluxed for 30 min. Removal of solvent undervacuum followed by p.1.c. over silica gel furnished fuco-stenone, m.p. 95.5-96.5" (lit.,20 95-98').A24(as)-Fucostene (6) .-A solution of fucostenone 2o (800mg) in dry ether (100 ml) was added to a stirred solution ofcharacteristics. However, a similar reaction sequencewith brassicasteryl acetate (18) proceeded without anyselectivity and furnished 5 p ,6p-methylene-ergost-22-en-3p-01 (27), 24,24-dimethylcholesta-5,22-dien-3~-ol (36) ,5p,6p:22,23-dimethylene-ergostan-3@-01 (38), and (37).The mass spectrum of (36) had an intense peak at m/e369 (70 eV, 85; 15 eV 100) corresponding to a lossof C3H7 presumably due to highly favoured fission of theC-24-C-25 bond and at m/e 271 representing the loss ofthe side chain and two hydrogens.17 In addition then.m.r.spectrum of (36) contained a singlet at 6 0-87(6H) (24,24-dimethyl) consistent with the proposedstructure. There is precedent for this type of carbenereact ion. l5The n.m.r. and mass spectra of (37) were identicalwith those of natural demethylgorgosterol (2).3 How-ever there were substantial differences in optical rota-tion and gas chromatographic retention time thusshowing that the natural (2) and synthetic (37) productsmust differ in the stereochemistry at position 22 and 23.EXPERIMENTALM.p.s were determined with a Kofler hot stage apparatus.U.V.spectra were recorded in 95 ethanol with a Carymodel 14 spectrometer; i.r. spectra were obtained forsolutions in chloroform or as potassium bromide pelletswith a Perkin-Elmer 42 1 spectrometer. N.m.r. spectrawere obtained with 2Hchlor~form as solvent and tetra-methylsilane or chloroform as internal reference on a VarianHA- 100 spectrometer. Optical rotations were recordedwith a Perkin-Elmer model 141 spectropolarimeter forsolutions in chloroform; 0.r.d. and c.d. curves were de-termined for solution in dioxan by Mrs.R. Records with aJASCO o.r.d./u.v. 5 spectrometer with c.d. attachmentLow resolution mass spectra were obtained by Messrs.R. G. Ross and R. Conover with an A.E.I. MS9 and Atlas2O E. R. H. Jones, P. A. Wilkinson, and R. H. Kerlogue, J .Chem. SOG., 1942, 391.liquid aiiimonia (100 nil) and lithium 21 (300 mg). After40 min the mixture was quenched with t-butyl alcohol-ether followed by ethanol (10 ml) until the blue colourdisappeared. The residue after evaporation of sninioniawas partitioned between ether and water. The ether layerwas washed with water and subjected to Jones oxidationfor 5 min. Chromatography of the resulting productfurnished pure A24(28)-fucosten-3-one (235 mg), m.p.137-138.5". Wolff-Kishner reduction of A24(2*)-fucosten-one furnished A24(28)-fucostene 5a-stigmast-24(28)-ene)(6), m.p.74-75' (40 yield), 6 0.68 (s, 18-H3), 0-75 (s,19-13,), 1-55 (d, 29-H,), and 5.22 (m, 28-H), un/e 398 (M+),383 (M - CH,), 300 (M - C,HI4, loo), 285, 257 (M-sidechain + 2H), 244, 231, 217, 218, and 203.Cavbene Additions to A24(2s)-Fucostene.-To a solutionof A24(28)-fucostene (6) (146 mg) in dry tetrachloroethylene(3 ml) and diethylene glycol dimethyl ether (0.75 ml) wasadded sodium trichloroacetate (500 mg) . The mixturewas heated under reflux for 1 h; two 200 mg portions ofsodium trichloroacetate were added and after furtherrefluxing for 30 and 45 min, the mixture was poured intowater and extracted with chloroform. The chloroformextract after chromatography over silica gel furnishedthe dichlorocarbene adduct, 24,28-dichloromethylene-5a-stigmastane (7) (122 mg), m.p.112.5-114' (from MeOH),6 0.65 (3H, s, lS-H,), 0-78 (s, 19-H3), and 1-17 (d, J 6 Hz,26- and 27-H,), m/e 480-482 (M+), 444-446 ( M -HCl),CH,), 257 (M - side chain + ZH), and 217 (ring Dcleavage + 1H).A solution of the dichloro-adduct (7) (120 mg) in dryether (20 ml) was added to a solution of lithium (100 mg)in liquid ammonia (50 ml). The mixture was stirred for1 h and quenched with ethanol (10 ml) and ether (20 ml).After evaporation of ammonia, the residue was partitionedbetween ether and water. The residue from the etherlayer on repeated crystallization from methanol-etherfurnished the cyclopropane adduct, 24,28-methylene-5~21 D.H. R. Barton, D. A. J. Ives, and B. R. Thomas, J . Chem.SOC., 1964, 903.370 (M - CHSCH=CCl2), 300 (M - C,H,,Cl,), 285 (300 1974 913stigmastane (S), m.p. 80-82O, a,21 +19" (c 0*55), 60.25-0.45 (cyclopropane H), 0.65 (s, lS-H,), 0.76 (s,19-H,), and 0.79 (d, J 6 Hz, 26- and 27-H,), m/e 412 (M+,(300 - CH,), and 217 (ring D cleavage + 1H).A solution of A24(28)-fucostene (6) (185 mg) in ether(10 ml) was added to the organozinc prepared from aZn-Cu couple (135 g) and di-iodomethane (5 g) in ether(50 ml) and the mixture was refluxed for 100 h. Work-upin the usual fashion followed by p.1.c. furnished startingmaterial (163 mg) and the cyclopropane steroid (8) (20 mg) .Simmons-Smith Reaction with Brassicasterol ( 19) .--Zinc(45 mg) and copper(1) chloride (120 mg) were refluxed underN, in ether (3.5 ml) for 15 min.Brassicasterol (ergosta-5,22-dien-3P-ol) (20 mg) was then added followed byCH,I, (10 p1) and the mixture refluxed for 48 h under N,.Only starting material was recovered after the usualwork-up.A solution of i-brassicasterol acetate (3a,5-cyclo-5a-ergost-22-en-5P-yl acetate) (5a) (500 mg) in ether (15 ml)and di-iodomethane (2-0 ml) was added to a suspension(refluxed prior t o addition for 30 min) of zinc (2-8 g) andcopper(1) chloride (0.4 g) in ether (10 ml). The mixturewas worked up after 48 h and consisted essentially only ofstaring material (analytical g.1.c.).5P, 6~-DichloromethyZene~hoZestan-3~-yZ Acetate (20) .-To asolution of cholesteryl acetate (9) (2.0 g) benzyltriethyl-ammonium bromide (0.2 g) in chloroform (30 ml) was addeddropwise with vigorous stirring 50 sodium hydroxide(20 ml). The mixture was stirred for 96 h at room tem-perature, poured into water, and extracted with chloroform.The extract after washing with water was dried oversodium sulphate and evaporated to furnish a pale gum.Column chromatography over Florisil using benzene-liexane as eluant furnished the pure dichloro-adduct(20) (60), as an oil, m/e 510-512 (M*), aID2l -40.6'(c 0*62), 6 0.63 (s, lS-H,), 0.84 (d, J 6 Hz), 1.25 (s, 19-H3),2.05 (s, Ac), and 5.00br (lH, CH-OAc).Benzyltriethyl-ammonium bromide was prepared by reaction of equi-molar amounts of triethylamine and benzyl bromide inacetone. The yield of dichloro-adduct (20) was insensitiveto the amounts of the catalyst (0.2-0.4 g) and chloroform(30-60 ml) .5P, 6P-MethyZenechoZestan-3P-oZ (2 1) .-To a solution ofsodium (1.2 g) in liquid ammonia (125 ml) was added thedichloro-adduct (20) (800 mg) in ether (60 ml).Themixture was stirred for 3 h and quenched with solid animon-ium chloride. After evaporation of ammonia, the residuewas partitioned in ether-water. The dried (Na,S04)ether layer was evaporated and acetylated with aceticanhydride-pyridine and the resulting acetate chromato-graphed over alumina (grade 11). Elution with hexane-benzene (3 : 7) furnished pure 5P,6P-methylenecholestan-3P-yl acetate (22) which on subsequent saponificationfurnished 5~,6~-methylenecholestan-3~-01 (21) in 60yield, m.p.98-100; aID21 -5-0 f 1' (1it.,l6 m.p. 101-102", a,20 -3.0"). Jones oxidation of (21) followed bycrystallization from methanol-acetone-water furnishedthe corresponding ketone (23), Mi 398, m.p. 72-73"7u,8a-DichlorornethyZene-5a-cJioZestan-3~-yZ Acetate (28).-The adduct (28) was obtained in 80 yield and purified asdescribed for (20); m.p. 129-130" (needles from methanol),a,21 -46.4" (c 0, 112), Mi 510, 512, 6 0.82 (s, lS-H,),0-86 (d, J 6 Hz, 26- and 27-H,), 0.89 (s, 19-H,), 2-00 (s,55y0), 397 (M - CHJ, 385 (M - C3H7), 355, 300, 285(iit.,19 75-77").Ac), and 4.65br (lH, CH-OAc) (Found: C, 70.0; H, 9 4 ;C1, 13.7. C,,H,,Cl,O, requires C, 70.1 ; H, 9.7 ; C1, 13.8).7a,8a-Methyl-5a-choZestan-3P-oZ (29) .-The dichloro-adduct (28) was dechlorinated with Na-NH, as describedfor (21) to furnish 7a,8a-methylene-5a-cholestan-3~-ol(29) in 70 yield, as a low melting solid, 6 -0.07 (t, J 4.0Hz), 0.25 (d, J 4.0 and 8.5 Hz), 0-75 (s, lS-H,), 0.81 (d, J6 Hz, 26- and 27-H,), 0.86 (s, 19-H,), and 3.43br (lH,CH*OH), m/e 400 (Mi), 385 (M - CH,), 382 (M -H20),367 (385 - H,O), and 287 ( M - side chain).Jones oxidationof (29) furnished the corresponding ketone (30), m.p. 148-149O (needles from MeOH), m/e 398 (M+), 383 ( M - CH,),285 ( M - side chain), 247, 244 (ring D cleavage), 243(ring D cleavage + lH), 163, 149, 135, 107, 95, 93, 81, 69,55, and 43, 0.r.d. (c 0.35, dioxan) t$,,, +2375, +2093sh, $,,, 2024, and $I2,, -864, c.d. (c 0.35, dioxan)22,2 3-MethyZene-5a-ergostan- 6P-oZ (35) .-Dichlorocarbeneaddition to ergost-22-en-6P-01 (1 1) as described for (20)resulted in a poor yield 8-10~0) of adducts which afterpartial enrichment by column chromatography overFlorisil were directly dechlorinated with Na-NH, tofurnish a mixture of four compounds, only one of whichcould be isolated in pure state by preparative g.1.c.overOV 3 (3) and is tentatively assigned structure (35),m.p. 129-131, m/e 396 (M -H20), 381 (396 - CH,),298 (396 - C7H14 cleavage of cyclopropane), 283 (298 -CH,), and 255 (M - side chain +H,O).5P,6~-DichZovomethyZenestigmast-22-en-3~-yZ Acetate (24) .-Stigmasteryl acetate (12) under analogous conditions tothat for (20) furnished only one dichlorocarbene adduct(24) (yield 40-60y0), which on subsequent dechlorinationwith Na-NH, furnished 5P,6P-methyZenestigmast-22-en-3P-oz (25), m.p.118-120deg;, .IDa1 -16.9' (G 0.195), 6 -0.08(lH, dd 4-5 and 8.5 Hz), 0.32 (t, J 4.5 Hz), 0.64 (3H, s,18-H,), 0.85 (d, J 6 Hz, 26- and 27-H,), 0.88 (s, 19-H,),3.86br (lH, CWOH), and 5.06 (2H, m), m/e 426 (Mi),408 (M - H,O), 328, 314, 287 (M - side chain), 285(M - side chain + 2H), 269 (287 - H,O), 245 (ring Dcleavage + lH), 149, 139, 125, 121, 107, 97, 95, 83, 69,and 55 (Found: M+, 426.38690. C,,H,OO requires amp;I,426.38615). Jones oxidation of (25) furnished 5P,6p-methylenestigmast-22-en-3-one (26), transparent in U.V.in both basic and neutral medium, m.p. 116-118', m/e424 (Mi), 381 (M - C,H7), 326, 312, 285 (M - side chain),283 (M - side chain + ZH), 199, 123, 97, 95, 83, 69, and55, 0.r.d.(c 0.19, dioxan) +5584, f5584,+I,,, +2856sh, and -4284, c.d. (c 0.19, dioxan)PI294 3-2388-el,,,., + 3660sh, O,,, + 6873, ~,,, + 6750 @in), andel,,, 4-7051.7a,8u-DichZoronzethyZene-5a-e~gost-22-en-3~-yZ Acetate (31).-Dichlorocarbene addition to 5a-ergosta-7,22-dien-3P-y1acetate (17) in an analogous manner to (20) furnished theadduct (31) (80), -66.5' (G 0.305), Mi 468-470,which on subsequent dechlorination with Na-NH, followedby acetylation and multiple crystallization from methanolfurnished 7a,8a-methyZene-5u-ergost-22-en-5P-yZ acetate (32),m.p. 141-143, M' 454, m/e 394 (M - CH,CO,H),+2-6" (c 0.84) (Found: C, 80-2; H, 10.9. C,lH,,02,0~5-CH,OH requires C, 80.3; H, 11.10).Saponification of(32) gave 7a, 8a-methylene-5a-ergost-22-en-3P-02 (33), m.p.137-139', f16.3" (c 0.222), S 0.00 (lH, t, J 5 Hz),0.28 (lH, dd, J 5-0 and 9.0 Hz), 0.84 (s, lS-H,), 0.87 (d, J6 Hz, 26- and 27-H,), 0.90 (s, 19-H,), 3-55 (lH, m, CWOH),and 5.20 (2H, m, 22- and 23-H), in/e 412 (M+), 397 (A4 914 J.C.S. Perkin ICH,), 315, 285 (M - side chain + 2H), 269 (287 - H,O),135, 125, 122, 109, 107, 97, 83, and 69 (Found: C, 83.1;H, 11-5. C,,H,,O,O.BCH,OH requires C, 82.7; H, 11.7)(Found : M+, 412.37050. C2,H4,0 requires M , 412-37050).Jones oxidation of (33) furnished 7a,8a-metlzyZene-5a-ergost-22-en-3-one (34), m.p. 162-164" (needles from MeOH),Mf 410, 0.r.d. (c 0-51, dioxan) C$,,, +2091, $I,,, + 1865sh,+a08 +1833sh, +804sh, and C$2,0 - 1126, c.d.(c 0.51,dioxan) euro;I,,, +2361 (Found: M+, 410.3530. C,,H,,Orequires M , 410.35485).Dichlorocarbene Addition to Brassicasteryl Acetate (18) .-Brassicasteryl acetate (1 8) was prepared from ergosterolaccording to Thomson et al. J22 except that tosylation wascarried out at O", solvolysis of the tosylate was effected atreflux for 5 min in buffered acetone, and excess of acetonewas removed under vacuum. The crude i-alcohol wasdirectly oxidized and the resulting 3a,5a-cyclo-A'-6-ketonewas purified by repeated crystallization. Lithium-am-monia reduction of 3a,5a-cycloergosta-7,22-dien-6-one for30 min furnished 5a-ergost-22-en-6P-01, m.p. 120-122",Mf 400, 6 0.69 (s, 18-H3), 0-81 (d, J 6 Hz, 26- and 27-H,),1-01 (s, 19-H,), 3-80 (W, 7 Hz, CH-OH), and 5.25 (2H, m,22- and 23-H), which on acetylation furnished the oilyacetate (1 1).Addition of dichlorocarbene t o brassicasteryl acetate(18) in the manner described for (20) furnished a complexmixture of adducts which after enrichment by columnchromatography over Florisil was directly dechlorinatedwith Na-NH,.The crude mixture was acetylated andthe corresponding acetate fractionally crystallized tofurnish a three-component crystalline mixture ( 18) (50),(36) (21), and (37) (18) acetates and a supernatantcomposed of two major components (27) (50) and (38)(20) acetates. Final separation was effected by pre-parative g.1.c. over OV 3 (3) on Gas Chrom Q. 5pl6p-Methylene-ergosten-22-en-3P-01 (27) had m.p.144-146"(needles from MeOH), 6 -0-06 (dd, J 5-0 and 8-0 Hz),0.32 (t, J 5.0 Hz), 0.64 (s, 18-H,), 0-85 (d, J 6 Hz, 26- and27-H,), 0.89 (s, 19-Hs), 3.85br (lH, CH*OH), and 5.14 (2H,m, 22- and 23-H), m/e 412 (M+), 397 (M - CH,), 394 (M -328, 314, 287 (IM - side chain), 285 (M - side chain +2H), 269 (287 - H20). 24,24-Dimethylcholesta-5,22-dien-3P-01 (36) had m.p. 156-157", a,21 -44-1" (c 0-102),6 0.67 (3H, s, lS-H,), 0.84 (d, J 6 Hz, 26- and 27-H,), 0-87(s, 24-H,), 0.99 (3H, s, 19-H,), 3.50br (lH, CHoOH), 5.15(2H, m, 22- and 23-H), and 5.33 (IH, m, 6-H), m/e 412H,O), 309,300,273 ( M - side chain), 271,255 (273 - H,O),213, 159, 145, 133, 97, 81, 69, and 55. 22,23-Di-epi-23-de-methylgorgosterol (37) had m.p. 163-165", a,21 - 64.4"(c 0.09), 6 0.18 (m, cyclopropane H), 0.61 (s, 18-H3), 0.80and 0.99 (each d, J Hz, 21- and 24-H,), 0.87 (d, J 6-5 Hz,26- and 27-H3), 1-00 (s, 19-H,), 3.53 (m, CH-OH), and5.35 (m, 6-H), m/e 412 (M+), 394 (M - H,O), 379 (394 -271 (M - side chain + 2H), 83, 69, and 55 mass spectrumidentical with that of natural, (isolated from P. porosa)demethylgorgosterol . 5P, 68:22,23-Dirnethylene-ergostan-3p-01 (38) had m.p. 165-167" (coarse needles from MeOH),vn/e 426 (M+), 411 (M - CH,), 408 (M+ - H,O), 328(cleavage of 22,23-cyclopropane 19), 295, 285, 107, 95, 83,81, 69, 55, and 43, 6 -0.09 (dd, J 5 Hz), 0.38 (m), 0-56(s, 18-H3), 0.79 (d, J 5.5 H,, 24-H,), 0.88 (s, 19-H, and d, J6.5 Hz, 26- and 27-H,), 0.97 (d, J 5.5 Hz, 2l-H,), and 3.84(m, CH*OH).HZO), 379 (394 - CH,), 369 (M - C3H7), 351 (369 - HZ0(M'), 394 (M - HZO), 369 (M - C3H7, 86), 351 (369 -CH,), 328, 314 (loo), 299 (314 - CH,), 281 (299 - HZO),Financial assistance from the National Institutes ofHealth is gratefully acknowledged.3/2218 Received, 29th October, 1973122 M. J. Thomson, C. F. Cohen, and S. M. Lancaster. Steroids,1965, 5, 745
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