1976 1165Crystal and Molecular Structure of Compactin, a New Antifungal Meta-bol ite f rorn Penicillium brevicompactumBy Alian G. Brown and Terry C. Srnale, Beecham Pharmaceuticals Research Division, Brockham Park,Trevor J. King, Department of Chemistry, The University, Nottingham NG7 2RDRainer Hasenkamp and Ronald H. Thompson, Department of Chemistry, University of Aberdeen, OldBetchworth, Surrey RH3 7AJAberdeen AB9 2UE. ScotlandThe structure of compactin (I) (7- 1,2,6,7,8.8a-hexahydro-2-methyl-8-(2-methylbutyryloxy) naphthyll-3-hydroxyheptan-5-olide), a metabolite isolated from cultures of Penicilliurn brevicornpacturn, has been determinedby a combination of spectroscopic, chemical, and X-ray crystallographic methods.METABOLITES isolated previously from strains of Penicil-lium brevicompactum include mycophenolic acid andrelated compounds, the pebrolide sesquiterpenes, and thebrevianamides.We describe here a new compound,compactin (I), which was isolated from a culture believedto be Penicillium byevicom$actt.m and was detected byits antifungal activity.2Compactin, C,H,O,, is optically active and shows U.V.absorption typical of a transoid conjugated diene. Thei.r. spectrum shows hydroxy and lactone absorption,consistent with the formation of a benzoate, and thesolubility of compactin, which is neutral, in aqueousfor the 8-lactone (111), from Ce$haZos$ovium ~ e c i f e i , ~ andcryptocaryalactone (IV), from the roots of Cryptocaryabo~rdilloni,~ respectively.The 1H n.m.r. spectrum of compactin (I) at high fieldshows two methyl doublets at 8 1.13 and 0.90 (each withJ 7 Hz) and a methyl triplet at 6 0.88 ( J 7.5 Hz) ascribedto the ethyl group.Both doublets collapse to singlets onirradiation at 8 2.37, indicating the presence of either anisopropylidene (Me,CH) group with non-equivalentmethyls or two ethylidene (CH,*CH) groups, themethine carbon atom(s) being adjacent to a carbonylgroup or a carbon-carbon double bond. A study of the6 .O br Im)4 0 IMe 0.901d)H 5.71 (dd)5.541ml H ti 5.951ddl1 1 1sodium hydroxide and its recovery on acidification.The carbonyl band at 1 710 cm-l (in KBr) is shifted to1724 cm-l in chloroform solution, and later work (seebelow) showed that this must arise from an ester group.The five oxygen atoms in compactin are thus identified.The 8-lactone system in (I) was identified from the lHn.m.r.assignments shown and appropriate decouplingand exchange experiments, and by dehydration to thea@-unsaturated lactone (11) in the i.r. spectrum of whichthe carbonyl absorption had moved to 1 730 cm-l. Theanhydro-compound (11) was first obtained in an attemptto prepare a P-bromophenylsulphonyl derivative, andwas also made by heating compactin with potassiumhydrogen sulphate in dimet hylformamide. The relevantspectroscopic data for (I) and (11) agree well with thoseW. B. Turner, ' Fungal Metabolites,' Academic Press,M. Richards, A. R. Clare, C. Reading, and M. S. Verrall, inLondon, 1971.preparation.60 and 100 MHz n.m.r.spectra revealed that the methyl-ene protons of the ethyl group are strongly coupled to2 . 6 4 H 5.996'83I4.55 H CHj CH.CH:CHPhC 0 2 Mecmr (IP)another adjacent group; thus the unit CH,*CH,*CH,- orCH,*CH,*CH must be present. Combining the latterwith an ethylidene group next to a carbonyl gives thefragment CH,*CH,*CHMe*CO-. That this is derived3 R. F. Vesonder, F. H. Stodola, and W. K. Rohwedder,4 R. T. Govindachari and P. C. Parthasarathy, TetrahedronCanad. J. Biochem., 1972.50, 363.Letters, 1971, 34011166 J.C.S. Perkin Ifrom a 2-methylbutyric acid unit, as suggested by themass spectrum, was subsequently confirmed by an acid-catalysed elimination reaction from which it was isolated.Hence compactin contains the ester group shown in (I).The presence of a transoid diene system was confirmedby extensive n.m.r.evidence, and decoupling experi-ments established its relationship to the rest of themolecule, but were difficult to interpret. The problemwas resolved by the 13C n.m.r. spectrum, which con-firmed the presence of four vinylic carbon atoms in com-pactin, the signals from three of which (at 132, 128, and123 p.p.m.) are doublets in the off-resonance decoupledspectrum whereas the fourth (at 133 p.p.m.) is a singlet.The 13C n.m.r. spectrum also confirmed the presence oftwo carbonyl carbon atoms (176 and 170 p.p.m.), andrevealed the existence of three sp3 carbon atoms attachedto oxygen (76, 67, and 62 p.p.m.) which appeared asdoublets in the off-resonance decoupled spectrum.Twoof these Y H - 0 - groups have already been identified inthe lactone system, and the third must carry the esterside chain. Irradiation at 3 038 Hz (6 5.33) caused col-lapse of the signal at 67 p.p.m. to a sharp singlet, at thesame time reducing the vinylic signal at 123 p.p.m. to abroad singlet. It follows that the broad lsquo; singlet rsquo; at6 5.33 in the lH n.ni.r. spectrum arises from the protonattached to the carbon atom bearing the ester group;this 6 value is unusually low. The other signal whichcollapses on irradiation at 3 038 Hz must be that of thevinyl carbon atom attached to the proton which resonatesa t 3061 Hz, Le. the proton which gives the broadlsquo; singlet rsquo; at 6 5.54, namely H-5rsquo;.Significant peaks in the mass spectrum of compactinare seen at m/e 390 (M+), 372 (M - H20), 288 (M -C,H1002), and 270 (M - H20 - C5H1,O,), which sup-port the presence of a C, ester unit as discussed above,and further major peaks at m / e 159 (C12H15), 158 (C12H14),gested a reduced naphthalene system.More convincingevidence was derived from the following chemical re-actions.Heating compactin in toluene with toluene-fi-sulphonicacid gave a viscous liquid, identified as a tetralin deriv-ative, C1,H2,02. From spectroscopic evidence it wasseen that the lactone ring had been dehydrated, and the2-methylbutyric ester group eliminated; the chromo-phore was now benzenoid and there was a methyl groupattached to the benzene ring. Owing to overlappingsignals from the vinyl and aromatic protons in the lHn.m.r.spectrum, the substitution pattern was not easilydiscernible but this problem was resolved by convertingthe tetralin into a naphthalene derivative by dehydrogen-at ion with 2,3-dichloro-5,6-dicyano- 1,4- benzoquinone(DDQ). In the n.m.r. spectrum of this compound thepattern of aromatic signals is identical with that of 1,2-dimethylnaphthalene (and different from those of theother isomers), showing that it is a 1,2-dialkylated naph-thalene. The chemical shift of the methyl group (6 2.50)is normal for p-methylated naphthalenes, and the otherside chain, containing the @-unsaturated lactone (in155 (C1amp;1), 145 (CIlHlJ, and 143 (C11HlI) (100) sug-agreement with the n.m.r. spectrum and the molecularformula), occupies the adjacent a-position.Thus thenaphthalene derivative has structure (VI), and thetetralin is (V). Some support for this was obtained byXI Irn 1synthesis of the lactone (VII) and its 6-methyl-2-naph-thy1 isomer, by condensing the appropriate methylnaph-thaldehydes with 4-acetylbutyric acid followed by hydro-genation. The n.m.r. spectra of these lactones, at highfield, showed a close resemblance to that of the dihydro-derivative of (VI).mo Yo HoPfo Yotnrrl cm1There remains the structure of compactin itself. Coni-bination of all the evidence cited leads to the indefinitestructure (VIII). As we did not have evidence to locatethe ester grouping unambiguously, compactin was sub-mitted to X-ray analysis (see Experimental section andTables 1-3), which established the structure and relativestereochemistry as in (I).The main modes of fragmentation of compactin underelectron impact are now evident.The M - H,O -C5H1002 ion has structure (IX), from which all the majorQ if)rsquo;(IXIa; m / e 145, 143, 129b ; m / e 159, 158c ; m / e 186, 185, 184ions between m/e 100 and 200 can arise by the cleavagesindicated. In the acid-catalysed conversion of com-pactin into the tetralin (V) the ring which becomesaromatic is not that from which 2-methylbutyric acid iseliminated. The subsequent hydrogen shifts are illus-trated in the Scheme, but need not occur in the ordershown1976 1167Biosynthetic studies have not yet been carried out oncompactin, but the compound is apparently polyketide-derived.Both the manner in which the nonaketidechain is folded and the low oxidation level are unusual inii*OHIP ISCHEMEcyclic polyketides. The ester side chain is not located atan ' expected ' position, and the oxygen at C-8' may havebeen introduced by autoxidation at an intermediatestage in the biosynthesis.EXPERIMENTALSpectroscopic measurements were made on solutions inethanol (u.v.), KBr discs (i.r.), and solutions in CDCl,(1i.m.r.) unless otherwise stated.Isolation of Compactin (I) .-Compactin,2 obtained byextraction of a culture filtrate of a strain of Penicilliumbrevicoinpucturn, had 1n.p. 152' (from aqueous ethanol)(Found: C, 70.85; H, 8.7; M+, 390.2403. c,3Hamp;requires C, 70.75; H, 8.8; M , 390.2406), $283"(c 0.84 in Me,CO), A,, 230, 237, and 246 nm (log E 4.28, 4.30,and 4.11), vwx.(CHC1,) 3 510 and 1 724 cm-l (lactone andester CO), vmS. (KBr) 3 520, 1 750 (lactone CO), and 1 710cm-l (ester CO), 6 5.95 (1 H, d, J 10 Hz, H-4), 5.71 (1 H, dd,J 10 and 5 Hz, H-3'), 5.44br (1 H, s, H-5'), 5.33br (1 H, s,H-S'), 4.62 (1 H, m, H-3), 4.35 (1 H, m, H-5), 3.28br (1 H, s,OH), 2.64 (2 H, d, J 4 Hz, H-6), 2.37 (2 H, m, H-2' andH-2"), 2.2-1.3 (14 H, ni, CH,, and CH), 1.13 (3 H, d, J7 Hz, 2"-Me), 0.90 (3 H, d, J 7 Hz, 2'-Me), and 0.88 (3 H, t ,J 7.5 Hz, CH,*CH,) ; m/e 390 (4), 372 (3), 288 (4), 273 (6),270 (12), 210 (14), 186 (12), 185 (42), 184 (57), 183 (24),169 (11), 159 (34), 158 (56), 155 (30), 145 (loo), 144 (40),143 (81), 129 (28), 91 (15), and 57 (31); benzoate, m.p.88-89" (from aqueous ethanol) (Found : M f , 494.2667.C,oH,806 requires M , 494.2668).An~ydroco~pactin.-(u) Compactin (200 mg) was heatedunder reflux with potassium hydrogen sulphate (150 mg) indimethylformamide (2 ml) for 6 h.After filtration thesolution was concentrated in zlacuo to give a brown oil whichwas chromatographed on silica gel in benzene-acetone(9 : 1). The least polar component crystallised from ethanolto give anhydrocompactin (11) (7-1,2,6,7,8,8a-hexahydro-2-methyZ-8-(2-snethylbutyrylo~y)naphthy~hept-2-en-5-olide~ asneedles, m.p. 118-122" (60) (Found: C, 73.5; H, 8.7;M-', 372.2303. C23H320, requires C, 74.2; H, 8.7; M ,372.2300), vmx. 1 730 cm-l; for 8 see formula (11), otherwisethe same as compactin.(b) Compactin (100 mg) in pyridine (1 ml) was treatedwith p-bromobenzenesulphonyl chloride (66 mg) at roomtemperature and left for several days.The red solution waspoured into ice-water and extracted with chloroform ; theextract was washed, dried (MgSO,), and concentrated invucuo to a syrup. This crystallised from ethanol t o give theanhydro-compound, m.p. 120-124' (73y0), identical (Lr.and n.m.r.) with that obtained in (a).7-( 2-Methyl-1-rcaphthyl) hefit-2-erc-boZide (VI) .-Compactin(100 mg) was heated under reflux in toluene (3 ml) contain-ing toluene-p-sulphonic acid (5 mg) . The solution was thenextracted with aqueous sodium hydrogen carbonate, dried,transferred to a silica gel column, and eluted with benzene-acetone (9 : 1).The tetralin (V), the least polar product,was isolated as a pale yellow, viscous liquid (60 mg) whichcrystallised from ethanol, m.p. 92-94' (Found : M+,270.1620. C18H,,0, requires M , 270.1619), A'nlax. 228, 276,285, and 293 nm (log E 4.94, 3.70, 3.74, and 3.60), v-.(CHCl, or KBr) 1700 cm-l, 6 7.0-6.7 (3 H, m, ArHand =CHCO), 6.02 (1 H, dt, J 10 and 2 Hz, CH,-CH=),4.50 (1 H, m, CH-0), 2.72 (6 H, m, ArCH,), 2.36 (2 H,ni, CH,*CH=), 2.29 (3 H, s, CH,), and 1.90 (6 H, m,ArCH,*CH,) ; in CDCamp;-C,D, (50 : 50) the aromatic protonsignals were clearly seen as a narrow quartet ( J 8 Hz).The alkaline extract was acidified and extracted withether; the organic layer was dried and evaporated leaving asharp smelling liquid, identified (i.r., n.m.r.) as 2-methyl-butyric acid by comparison with an authentic sample.The tetralin (V) (140 mg) was heated under reflux in drybenzene (5 ml) with DDQ (236 mg) for 24 11.After coolingand filtration, the least polar product was isolated bychromatography on silica gel in benzene-acetone (9 : 1). Itcrystallised from ethanol to give the naphthalene derivative(VI) as needles, m.p. 109-110" (32) (Found: C, 80.8; H,6.8; M+, 266.1306. C18H1802 requires C, 81.2; H, 6.8;M , 266.1306), Lx 228, 276, 285, 293, 308, and 323 nm (log~4.94,3.70,3.74,3.60,2.90,and2.70),v,,(KBr) 1705cm-1,6 8.1-7.3 (6H, m, ArH), 6.84 (1 H, ddd, J 10, 5, and 4Hz,CH,*CH=), 6.02 (1 H, dt, J 10 and 2 Hz, =CHCO), 4.52 (1 H,m, CH-0), 3.30 (2 H, m, ArCH,), 2.50 (3 H, s, CH,), 2.34(2 H, m, CH,-CH=), and 2.00 (2 H, m, ArCH,CH,), m/e266 (52), 171 (23), 180 (24), 179 (la), 155 (loo), 154 (68),and 141 (10).The lactone (VI) was hydrogenated in ethyl acetate overpalladised charcoal (10) at room temperature until 1 mol.equiv.of hydrogen had been absorbed. After filtration andevaporation the residue was chromatographed on silica gelplates in chloroform to give the dihydro-derivative as a gum(Found: M+, 268.1462. C18H,,0, requires M, 268-1463),vmX. 1735 cm-l, 6 8.1-7.3 (6 H, m, ArH), 4.42 (1 H, m,CH-0), 3.24 (2 H, m, ArCH,), 2.51 (3 H, s, CH,), 2.47 (2 HIm, CH,*CO), and 2.16-1.42 (6 H, m, CH,) .7-(8-Methyl-l-naphthyl)-5-oxohept-6-enoic A cid.-To 8-methyl-1-naphthaldehyde (1.02 g) and 4-acetylbutyricacid (0.98 g) in ethanol (15 ml) was added 2~-sodiumhydroxide (4.2 ml).The mixture was heated under refluxfor 1 h, cooled, diluted with water, acidified, and extractedwith ether. The extract was shaken with 2~-sodiumcarbonate; the aqueous layer was acidified and the preci-pitate transferred to ether; this solution was dried (MgSO,)and evaporated. The residue crystallised from methanol togive the acid as light yellow plates, m.p. 131-132" (33)(Found: C, 76.4; H, 6.7. CI8Hl8O3 requires C, 76.6; H,6.4y0), vmx. 3 400br, 1 731, 1 670, and 1 603 cm-l, 6 8.55 and6.48 (each 1 H, d, J 16 Hz, CH=CH), 7.7br and 7.4br (each3 H, m, ArH), 2.82 (3 H, s, ArCH,), 2.80 (2 H, t, J 7 Hz,=CH*CO*CH,), 2.48 (2 H, t, J 7 Hz, CH,-CO,H), and 2.06(2 H, m, CH,CH,*CH,).Hydrogenation as for (VI) gaveL. P. Zalukaev and V. V. Moiseev, Zhur. ovg. Khim., 1966,2,2821168the lactone (VII) as a gum, 6 7.8-7.2 (6 H, m, ArH), 4.45(1 H, m, CH-0), 3.40 (2 H, m, ArCH,), 2.92 (3 H, s, CH,),2.51 (2 H, m, CH,*CO), and 2.20-1.47 (6 H, m, CH,).7-(6-MethyZ-2-naphthyl)-5-oxohe$t-6-enoic Acid.-Thisacid, prepared as above from 6-methyl-2-naphthaldehyde,BJ.C.S. Perkin IMULTAN ? and the best E map revealed the position of allbut one non-hydrogen atom. The position of the missingatom was found from a difference map following two cyclesof isotropic block-diagonal least-squares refinement.Further refinement proceeded smoothly; all the hydrogenTABLE 1reference to the atom t o which they are attachedFractional co-ordinates of atoms ( x lo4) with standard deviations in parentheses.Hydrogen atoms are numbered withla-575(3)139(3)195(3)- 796(3)- 329(3)- 616(3)- 157(3)944(3)636(3)562(3)1658(3)1014(3)704(3)1524(3)- 925(56)- 349(61)- 1 012(68)- 1 419(48)-1 373(67)-1 171(67)260(67)1089(59)2 090(55)1617(49)1567(41)964(43)2 094(48)1037(45)1113(48)154(44)- 290(53)Y / b2 849(1)2 452 (1)1 922(1)1737(1)2 017(1)1 825(1)2 095(1)2 640( 1)2 893(1)2 636(1)2 311(1)3 372(1)3 710(1)4 252(1)2 959(21)2 673(23)1717(22)1417(19)1470(22)1784(22)2 245(26)2 808(23)2 361(21)3 175(19)2 385(16)3 607(16)3 238(18)3 494(17)3 846(21)4 471(18)4 793(17)ZIC7 499(3)6 171(3)6 491(4)7 832(4)9 138(4)11 861(4)11 607(3)10 268(3)8 898(3)8 663(4)7 292(3)5 917(3)5 903(3)7 577(60)5 315(70)5 742(63)7 965(53)10 568(66)12 560(60)12 331(77)12 609(67)11 516(58)10 203(52)8 662(45)8 066(45)7 365(60)5 017(47)6 960(59)6 876(61)4 730(46)10 473(4)formed light yellow leaflets, m.p.195-196' (from ethanol)(65) (Found: C, 76.4; H, 6.7. C,,H1,O, requires C, 76.6;H, 6.4), v- 3 400br, 1 700, 1 675sh, and 1 620 cm-l,6(CDCl, + 1 drop CF,*CO,D) 7.92 and 6.94 (each 1 H, d, J16 Hz, CH-CH), 7.82-7.23 (6 H, m, ArH), 2.98 (2 H, t , J7 Hz, =CH*CO*CH,), 2.60 (2 H, t, J 7 Hz, CH,*CO,H), 2.54(3 H, s, CH,), and 2.10 (2 H, m, CH,*CH,*CH,). Hydro-genation as for (VI) gave the 2,g-isomer of the lactone (VII)as a gum, 6 7.8-7.2 (6 H, m, Ar), 4.24 (1 H, m, CH-0), 2.93(2 H, m, ArCH,), 2.49 ( 5 H, m, CH, + CH,*CO), and 2.20-1.38 (6 H, in, CH,).Crystal Structuve Determination.-A fragment was cutfrom a large crystal of compactin of indeterminate shape.The cell dimensions and symmetry were determined byoscillation and Weisenberg photographs (Cu-K, radiation)and refined and confirmed on a Hilger-Watt four-circlediffractometer .Crystal data. C,,H,,O,, M = 390.Orthorhombic, u =9.728 (I), b = 24.030 (2), c = 9.185 (1) A, U = 2 147 A3,D, = 1.20, D, = 1.207 g cm-s, 2 = 4, F(000) = 848. Spacegroup P2,2,21 (from systematic absences) ; p(Mo-K,) =0.90 cm-1.Intensity measurements were made by 20--w scans out to6 = 30" (monochromatic Mo-Ka radiation) and 2 179 re-flections with a net count 3a were deemed observed. Thestructure was solved by using the direct methods programG.Germain, P. Main, and M. M. Wolfson, Acta Cryst., 1971,6 L. Syper, Tetrahedron Letters, 1967, 4193.A27, 368.X l a1242(3)2 293(4)3 708(4)4 024(3)- 720(3)-2 152(4)-2 260(5)-2 509(6)-2 378(7)- 709(2)305(2)2 966(2)5 150(3)2 191(3)1307(63)1994(68)4 619(40)3 785(72)2 167(46)2 274(56)1669(57)-2 795(50)- 3 261 (102)-2 097(85)-1 424(79)-3 667(68)-1 865(77)-2 924(101)-2 851(92) - 1 251(84)3 176(80)Y lb4 621(1)5 087(1)4 833(1)4 394( 1)3 689( 1)4 131(2)4 364(2)4 180(2)3 162(1)3 956( 1)4 088(1)4 278(1)6 404( 1)4 345(24)5 350(25)6 118(16)4 647(28)2 720(19)2 129(21)3 569(18)4 308(38)3 804(35)4 435(30)4 435(26)4 695(30)3 767(37)4 141(32)6 680(29)3 901 (1)2 021(21)4 444(33)zlc4 603(3)4 519(4)4 379(4)5 492(4)10 949(4)11 204(6)12 775(6)10 109(7)8 648(7)10 470(2)11 157(3)6 017(3)6 879(4)5 836(3)3 611(69)3 593(74)4 359(45)3 351(77)5 278(52)6 494(68)4 758(60)11 199(63)12 907(111)13 647(10)12 787(88)10 276(77)10 114(87)8 523(109)7 850(96)8 237(92)6 lOl(87)atoms were located from difference maps and their para-meters were allowed t o refine isotropically for four cycleswith the other atoms varying anisotropically.A weightingFIGURE 1 Compactin : interatomic distances, bond angles,and crystallographic numberingscheme of the form w = 1 for F, 22.0 and w = (22.0/F0)2for the stronger reflections was then employed for fina1976 1169refinement by full matrix methods with the hydrogen atomsfixed and reflections (30) with WAF 2.0 not contributingto the shifts.A t convergence, R was 5.2.TABLE 2Interatomic distances acd angles(a) Bond lengths in A, with standard deviations in parentheses; an asteriskdesignates an atom in another molecule1.549(4)1.544(4)1.531 (4)1.07(5)1.507(4)1.538 (4)1.09( 6)1.327(5)0.95(6)1.448( 5)0.99(6)1.339(5)1.535(4)1.49946)1.13( 5)1.531 (5)1.07(5)1.14(7)1.523(4)1.06(6)1.20(5)1.525(4)E!i1g((3) C(8a)-H(CSa)C( 9)-H(C9)C( 9) -H'(C9)C( 9) -H"(C9)C(lO)-c(ll)C(10)-H(C10)C(l0)-H'(Cl0)C( 11) -C( 12)C(ll)-H(Cll)C( 11)-H'(Cl1)C(12)-C(13)C(12)-0(3)C(12)-H(C12)C(13)-C(14)C( 13)-H (C13)C(13)-H'(C13)C( 14)-C( 15)C(14)-0(5)C(14)-H C14)0(5)-H(65)1.471(3)1.17(5)1.07(4)1.15(5)1.07(5)1.08 ( 5 )1.531(4)0.91(4)1.10(6)1.528(4)1 03 41:02l5{1.513(4)1.461(4)1.11(5)1.518(4)1.14(4)1.13 (6)1.511(5)1.432(4)1.10(7)1.08 (8)C(15) -C f 16)C(15) -H (C15)C( 15)-H'(C15)C(16)-0(4)C(16)-0(3)Of1 I-CflB1CilBI-OI2jCjlBj-Ci2.B)C(2B)-C( 3B)C(2B)-C(4B)C(2B)-H(C2B)C(4B) -C( 5B)CfHB)-HCHB)C( HB j -H (CHB)C(JBkH(CBB1C(3Bj-H;(C3BjC(!B)-H"C(3B)C(oB)-H(C5B)C(BB)-H'(CIB)C(5B)-H"(CzB)H(05)-0(21 o(")-O(zj *1.501(5)1.12(4)1.05(7)1186(41:354(41.341(3)1.201(4)1.501 (5)1.54917)1.540(6)1.01(5)1.506(8)1.15(7)1.01(7)1 07 10)1:079)1.09(8)1.1 3( 9)1.01 (8)1.14(8)1.85(8)2.896(4)(b) Bond angles in degrees, with standard deviations in parentheses; an asteriskdesignates an atom in another moleculec(9j-cja j-cii jC( 1) -C( 2) -H (C2)C(3)(2)-H(C2)C f 91 -Cf21-H f C2 Ic(ij-C(3j-~3(4) 'C(2)-C(3)-H(C3)C(3)(4)-H(C4)Cf4a)-C(4)-H(C4)C(7j-C(6)-H(C6)'C(7)-C(G)-H'(C6)H(C6)-C(6)-H'(C6)Cf61(7)-CiS)C(l)'C(S'a)'H(da)C(2)(9)-H(C9)Cf21fgI-H'fC91C(ll)d(lO)-H'(ClO)H(ClO)-C(lO)-H'(ClO)c(10)-C(11)-c(12)C(lO)-C(ll)-H(Cll)C(lO)-C(ll)-H'(Cl1)110.3(2)104(3)llO(3)110.4( 3)109.6(3)114.3(3)105(3)108(3)llO(3)123.0(3)121(3)115(3)124.3( 3)118(3)117(3)122.2( 3)115.8(3)122.0(3)124.6(3)117(3)118(3)112.4(3)109(3)102(3)lOS(3)116(3)109(5)112.0(3)113(3)114(2)109(3)109(3)99(4)111.2(2)108.5 (2)108.0(2)102 2)10912)118(3)115.2(2)111.4(2)111.4( 2)108(2)106(2)l04(2)108(2)113(3)112(3)109(4)109(4)107(4)11 5.4( 3)113(3)108(3106(2{113 2101141110.9(2)109(3)llO(2)OjlJ-C(lBj-o(2) 'C(2BI-CflB1-0(21C(2Bj-C(3Bj-H'(C3B)C( 2B) -C( 3B)-H"(C3B)H(C3BICf 3BI-H'IC3BIlOS(2)114.3 3)105.712)112.9(2)115 2)10712)110.5(3)102(2)llO(4)108.7(2)107.6(3)110.5(3)107(3)114(3)109(3)114.4(3)118 2)10814)106(2)107(4)101/4)124:0/3)117.9 3)123.9(2)llO(4)117.6(2112.3(2123.4(3124.4(3)109.3(3)110.6 (3)109.6(3)108(3)104(3)115(3)108(5)llO(5)lOl(4)111(7)114(6)112(6)113.0(4)104(3)115(4)105(4)lOO(5)119(5)104(5)112(5)llO(4)118 0 3)163(6)168(2)Figure 1 shows the structure and the crystallographicnumbering with bond lengths to three significant figures andangles to the nearest half degree.The atoms of the butyratechain are less well defined than the others and have highertemperature factors. The estimated standard deviations ofbond lengths were ca. 0.004 A, and of angles 0.25", except forthe butyrate carbon atoms which have errors approximatelytwice these values. All dimensions involving hydrogen arewithin 3 c of expected values. Full details of all atomic co-ordinates, bond lengths and angles, and thermal parametersare given in Tables 1-3.Observed and calculated struc-TABLE 3Thermal parameters(a) Anisotropic, in the form e~p--2n'(U~,a*~h~ -t Uz2b*'ka + Ut3c*'l: + 2 4a*b*hk + 2Ulla*c*hl + 2U,.b*c*kl), multiplied by lo', with standard deviations inparenthesesAtom Val US, Us. U1r u1, u.1378(14) Eii 462(15C(3) 531(181446(17)299(13)C(8a) 325(12)C(9) 496(17)488(16) ::?! 534(17)453(15) Eli: 548(18)578(19)583(20)C 16) 507 17)ClB 419 15)C2BI 50dl8)C13B) 846(32)769(301297(49{O(1) 342 10)50013)456(11)442(18) $: 669(14)(b) Isotropic, multiplilAtom2l(l4)H(C5) 48(19)16(14) :) 24(11)294(12)360(14)317 12)386i14)600(17)535(17)368(13)316(11)596 18)351113)343(13)411114)343 12)913(30)630(23)1129 39)33119)880(18)390(10)ed by 10'A42 9 (i4)656(20)55 1858amp;{5 3 2 (18)475(17)464(16)410(14)464(18)412(15)420(15)400(15)417(16)425(16)469(17559(19{660(18)926(27)1 142(391331(43{1106(42)556 129341193580(13)1071(23)5 76( 13)tom-49(11)-73(13)-29(13)-102(13)-31(15)-79 15)-14(11)-120(13)-86(13)-48(12)-79(14)-17{11)-12(15)-22(14) - 32(27)181 22)-21 i 8)-118(10)-31(9)-75(13)324 38)-82(11)UHfClOi 2 9 h jH'(ci6) i6ii3jH(Cl1) 29(12)H'(C11) 30(16)H(C12) 25(13)H(C13) 13(11)H'(C13) 30(16H(C14) 58(23{-51(12) - 44( 14)-51(17)3 ( W74(14)54(15)36(16)-48(14)-10(13)7 ( W65(16)-87(14)-107(15)-24(14) - 74(15)8 ( W96(16)3(17)4(15)62(20)329(32)119(30)-484(40) y:; -35(11)-122(16)99(13)AtomH(C15)H'(CI5)H(C2B)H(C3B)H'JC3B)H' (C3B)H(C4B)H'(C4B)H(C5B)H'(C5B)H"(C5B)H(O5)-3 12)-814)--31(15{29(13)116 14)127tlb)86(16)32(12)22 12) -islie)62 12)4312)42(12)70(14)49 13)2315)-10318j 3 1490(2898 351 - 309)99(11)227(19)-72(14-51(15)-364 31)-113(14)-68(11)U14(10)86(26)141(39)90(30)92(24)137(30)147(42)116(36)117(33)86(28)bFIGURE 2 Compactin: relative configurationture factors are listed in Supplementary Publication No.SUP 21719 (13 pp., 1 microfiche).*The hydrogen of the hydroxy-group of the lactone ring isca.1.85 from the carbonyl oxygen atom of the butyrategroup of the adjacent molecule, suggesting that there ishydrogen bonding in the crystal between these two oxygenatoms. No other intermolecular distances are significantlyshort.* For details of Supplementary Publications see Notice toAuthors No. 7 in J.C.S. Perkin I , 1975, Index issue1170 J.C.S. Perkin IFigure 2 is a sketch of the molecule showing its shape and of compactin; to Mr. A. E. Bird for analytical and spectro-scopic data; and to Dr. G. A. Garton (Rowett Institute) fora sample of 2-methylbutyric acid. One of us (R. H.) isgrateful to the Dr. C. Duisberg-Stiftung for financial sup-5/1471 Received, 35th Jut?, 19751the relative configurations of the chiral centres.We thank Dr- 1. Sadler for l3C n.m.r. spectra and Dr- J.Feeney for 100 MHz decoupled n.m.r. spectra. We are port.grateful to Dr. M. Richards and Mr. M. Verrall for the suppl
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