1366 J.C.S. Perkin IThe Chemistry of Fungi. Part LXVIII.l The Absolute Configuration of(+)-Sclerotiorin and of the AzaphilonesBy W. Basil Whalley,' The School of Pharmacy, The University of London, London WC1 N 1AXGeorge Ferguson, Wayne C. Marsh, and Roderic J. Restivo, Department of Chemistry, The University,X-Ray crystallographic examination of N-methylsclerotioramine, derived from (+) -sclerotiorin, has defined theabsolute stereochemistry of the derivative and hence that of (+)-sclerotiorin and of the other members of theazaphilone group of fungal metabolites.From an X-ray crystallographic examination we havenow defined the absolute stereochemistry of N-met hyl-2 F. C . Chen, P. S . Manchand, and W.B. Whalley, J. Chenz.Soc. (C), 1971, 3677.Guelph, Ontario, Canada N1 G 2W1WE have previously deduced the relative stereochemis-try of the azaphilone group of fungal metabolites.P.S. Manchand, W. B. Whalley, and Fa-ching Chen, Phyto-chemistry, 1973, 12, 2631 is regarded as Part LXVII of this series1976 1367sclerotioramine 3 as illustrated in formula (1; R = Ac,X = NMe). The course of the analysis is described inthe Experimental section and a view of the molecule,giving the crystallographic numbering scheme, is shownin Figure 1. A view of the molecular packing viewedalong the b axis is given in Figure 2. Because of theFIGURE 1 View of N-methylsclerotioramine showing thecrystallographic numbering schemerelatively large estimated standard deviation of the bondlengths, a result in part of the fairly high thermal motion,especially in the heptadiene side chain, none of theobserved bond lengths or angles listed in Table 2 differssignificantly from expected values.4 The intra-annulartorsion angles in Table 3 reveal that ring A adopts aconformation close to a half-chair, and ring B is essentiallyplanar. The bond lengths and angles involving N(l)(Figure 1) indicate that this atom is sp2-hybridized andtakes part in the extensive conjugated system.Theseconformational conclusions are similar to those deducedTABLE 1Fractional co-ordinates ( x lo4) with estimated standarddeviations in parenthesesxla-0 606(3)2 238(7)1990(7)1232(7)3 434(6)0 272(9)1 629(11)2 606(9)1647(9)0 104(8)-1 948(7)-0 667(10)-2 498(9)-1 796(10)-0 446(9)-2 721(14)2 649(11)3 616(11)-3 816(10)-4 478(11)-6 728(10)-6 304(10)- 7 629(14)-8 908(18)-9 700(24)-6 934(23)-6 277(17)3 650(13)YlbO *-1 027(12)4 764(13)0 096(13)1173(10)6 987(12)1608(16)0 718(18)2 332(16)3 926(16)4 674(14)6 292(15)5 945(16)4 166(16)3 353(16)8 867(21)0 077(18)6 890(18)6 998(21)6 849(18)5 687(20)6 047(31)4 695(28)5 098(49)8 979(27)3 613(22)-1 087(19)5 689(49) -ZIC2 138(1)3 087(4)4 642(3)4 684(3)4 184(3)3 440(4)2 815(4)3 166(5)3 662(4)3 991(6)3 697(4)3 786(6)2 860(6)2 663(6)3 OlO(4)3 708(7)4 636(4)6 165(5)2 426(6)1873(6)1401(6)0 898(7)0 338(8)1074(11)1639(8)3 233(6)0 439(9)-0 386(9)* Fixed to specify the origin in space group P2,.less than 3.5 A are listed in Table 4 and correspond tovan der Waals interactions.It thus follows that (+)-sclerotiorin, from which ourspecimen of N-methylsclerotioramine was derived, hasFIGURE 2earlier 5 on the basis of other spectroscopic and chemical the absolute configuration shown in formula (1 ; R = Ac,data.X = 0). Hence (+)-deacetylsclerotiorin (1; R = H,Those X = 0), rotiorin (2; R = H), 5-chlororotiorin (2; R =R. A. Eade, H. Page, A. Robertson, K. Turner, and W. B.F. M. Dean, J. Staunton, and W. B. Whalley, J. Chem. SOL,L. E. Sutton, CJtem. SOC. Special Publ., No. 18, 1966.View ol the molecular packing of N-methylsclerotioramineThere are no unusual intermolecular contacts.Whalley, J.Chem. SOC., 1957, 4913.1959, 30041368 J.C.S. Perkin ITABLE 2Bond lengths (A) and valency angles (") with estimated - -- standard deviations in parentheses1.720( 9)1.42(1)1.39( 1)1.24( 1)1.56( 1)1.45( 1)1.49(1)1.54( 2)1.23(1)1.48( 1)1.35(1)1.43( 1)1.34(1)1.37( 1)1.36( 1)11 9.2( 8)1 18.4( 8)122.4(8)1 16.1 (7)120.8(6)1 23.1 (8)1 2 7 4 9)1 1 7.5 (8)1 14.8 (9)108.8( 7)110.5(7)105.6( 7)1 16.1 (7)107.2(7)1 20.9 (8)121.9(8)117.0(8)120.6(8)118.8( 8)120.6(7)123.2 (8)108.2 (8)C(7)-C(13)N( 1 )-C( 10)C (8)-C (9)C ( 1 3)-C ( 1 4)C ( 14)-C ( 1 5)C( 15)-C( 1 6)C(15)-C(21)C( 16)-C( 17)C ( 1 7)-C (1 8)C(17)-C(20)C( 18)-c( 19)C(11)-0(3)C(l1)-C(12)C( 11)-0(4)N(l)C(7)C(8)C(8)C(7)C(13)C(7)C(8)C(9)C(l)C(9)C(6)C(l)C(9)C(8)C(5)C(9)C(8)0 (3 j C ( 1 1) 0 (4)C(7)C( 13jC( 14)C( 13)c( 14)c( 15)c (1 4) c ( 15) C(2 1)N (1) C( 7) C( 13)0(3)C( l l ) C ( 12)0(4)C( l l ) C ( 12)C (14) C (1 5) C( 16)C(16)C(15)C(21)C( 15) C( 16) C( 17)C( 16) C( 17) C( 18)C( 16) C( 17) C( 20)C( 18)C( 17)C(20)C( 17) C( 18) C( 19)C(3) O(4) c (1 1)1.49( 1)1.42( 1)1.48(1)1.31(1)1.47( 1)1.33(2)1.46(2)1.54(2)1.55(2)1.49 (3)1.24(1)1.35( 1)1.46(1)1.60(2)1 1 9.8( 8)118.4(8)1 2 1.8 (9)122.7( 8)122.6 (7)123.0(8)114.4(8)120.0(8)125.9(9)1 1 4.2 (8)123.9( 10)127.8(11)11 7.2( 11)1 17.5( 10)125.2( 11)128.8( 14)108.5 (1 4)110.9( 13)1 10.3 (1 5)11 3.3( 16)1 16.3 (6)TABLE 3Intra-annular torsion angles with estimated standarddeviations in parenthesesC( 9) C( l)-C( 2) C( 3)C (2) C( 3)-C(4) C( 5)- 15.2 ( 13)- 29.8( 1 1)C( 6) C( 5)-C (9) C(8)C( 6)N( l)-C( 6) C(5)C( 1) C( 2)-C (3) C(4)C (3) C (4)-C (5) C (9)C (4) C (5)-C (9) C (1)C(2) C( l)-C( 9) C( 5)30.8 (1 1)1 3.1 (1 1)3.7 (1 3)- 2.1 (14)C( 9) C (5)-C (6) N( 1)C (6) N (1 )-C (7) C (8)N (1) C (7)-C (8) C( 9)C( 7) C (8)-C(9) C (6)TABLE 4Intermolecular contacts less than 3.5 A0(1) * - - C(21I) 3.36(2) C(6) * * O(3II)O(2) - - * C(1111)O(2) * * C(12II) 3.18(1) O(2) * - * O(3v)C(6) - * * O(lI1)N(1) - * Cl(l11) 3.473(8) Cl(1) - - - C(7I'I)O(2) * * * O(3II) 3.44(1) C(10)-0(2V)3.42(1) O(4) - - - C(12Iv)3.42(1)2.0 ( 12)- 1.6(13)-1.7(13)- 3.6( 14)4.2(13)0.5(13)3.26(1)3.45(1)3.29(1)3.45(1)3.40( 1)Roman numerals as superscripts refer to the following trans-formations relative t o the reference molecule at x,y,z: I (1 + x,-1 + y , 2); I1 ( x , 1 + y, 2); I11 (x, -1 + y, 2); IV (1 - x,4 fy, 1 - 4 ; V(-x, 8 + y , 1 - 2).Cl), 5-chloroisorotiorin (3), and (+)-deacetylsclerotiorinorsellinate (1 ; R = orsellinyl), have the absolute con-figurations shown.Similarly, ankaflavin (4; R = n-C,H,,), monsacin (4; R = n-C,H,,), rubropunctatin (5;R = n-amp;HI,), monascorubrin (5; R = n-C,Hl5), rubro-rotiorin (6), mitorubrin ( 7 ; R = H),* mitorubrinol (7;R = OH), mitorubrinic acid ( 7 ; R = CO,H), (-)-sclero-* The orsellinyl residue in structures (6) and (7) in ref.2 isincorrectly formulated.tiorin (8; R = Ac), and (-)-deacetylsclerotiorin (8;R = H) have the absolute configuration shown.COMe0H O b M eOH0 ( 8 )EXPERIMENTALX-Ray Crystal Structure A naZysis of N-J4TethyZscZerotior-amine.-Crystals of N-methylsclerotioramine are deep redneedles elongated along the b axis. Preliminary cell para-meters and space group data were obtained from variousrotation, precession, and Weissenberg photographs ; accur-ate cell parameters were obtained by a least-squares pro-cedure applied to 12 general reflections measured on aHilger and Watts diffractometer.Crystal data. C,,H,,ClNO,, M = 403.9. Monoclinic,a = 8.756(2), b = 6.330(1), c = 19.367(6) A, p = 94.27(2)",(20 "C; Cu-K,; A = 1.5415 A, p = 18.1 cm-l).SpaceU = 1070.4 A ', 2 = 2, D, = 1.253 g CIII-~, F(000) = 421976 1369group P2,/un (C;*) or P2, (Ci) from absent reflections: OKO,k = 2n + 1 ; P2, from structure analysis.The intensities of all reflections with 28(Cu-K,) 140deg;were measured on a PDPS-I controlled Hilger and Wattsfour-circle diffractometer with a scintillation counter andapproximate monochromatic radiation (Ni filter and pulseheight analyser). A O/o step scan was employed with 0.01"steps, a counting time of 1 s per step, and a scan width of0.7" in 8. Background counts of 17.5 s were made a t thebeginning and end of each scan. The intensities of 3 stand-ard reflections, measured after every 50 reflections, de-creased over the course of the data collection to values whichwere 90 of the starting intensities, indicating some crystaldecomposition.The data were corrected for the decompo-sition (assumed linear between standards), Lorentz andpolarization factors were applied, and the structure ampli-tudes were derived. Of the 1 920 unique data, 786 reflec-tions had a net count of less than 3 c above background,where a(1) is defined by 02(I) = S + 4(B, + B2) + (0.05S)2 where S is the scan count and B, and B, are the back-ground counts and were excluded from the refinement.The structure was solved in a straight-forward manner, by using the multiple solution programMULTAX.6 The E-map revealed almost the entire mole-cule except for six atoms which were subsequently locatedfrom an (F, - F,) synthesis.Refinement proceededsmoothly. Isotropic f ull-matrix followed by block-diagonalanisotropic least-squares refinement gave an R value of* For details of Supplementary Publications see Notice toAuthors No. 7, J.C.S. Perkin I , 1975, Indexissue.G. Germain, P. Main, and M. M. Woolfson, Acta Cryst., 1971,A27, 368.Structure analysis.0.075. At this stage a difference map revealed the presenceof 23 of the 26 hydrogen atoms. The C(12) methyl groupappeared to be rotationally disordered. Inclusion of thehydrogen atoms in the structure factor calculation, but notin the refinement, gave a final R value of 0.058 for the 1 134observed reflections. The scattering factors for the non-hydrogen atoms, including the anomalous dispersion correc-tions for chlorine, were taken from ref.7 ; those for thehydrogen atoms were from ref. 8. The weighting schemeemployed in the final stages of refinement was that ofHughes a with w = 1.0 for F, 8.0 and w = (8.0/F,)2 forF,, 8.0. The relative validity of the weighting scheme,as judged by the variation of w(F, - F,)2 over ranges oflFol and sin e/A, was satisfactory. Final positional para-meters appear in Table 1. The observed and final calcu-lated structure amplitudes as well as the thermal parametersare listed in Supplementary Publication No. SUP 21739 (16pp.).* A structure factor calculation on the other enantio-morph yielded an R value of 0.060.The difference in the R value is small, and we would behesitant to argue strongly in favour of the configurationgiving R = 0.058 on this basis alone; however, this con-figuration, corresponding to the co-ordinates listed in Table1, follows from the absolute configuration already known 10of the asymmetric centre in the sicle-chain.5/2265 Received, 19th November, 19761' International Tables for X-Ray Crystallography,' vol. 111,R. F. Stewart E. R. Davidson, and W. T. Simpson, J . Chewlo G. A. Ellestad and W. B. Whalley, J . Chela. Soc., 1966, 7260.Kynoch Press, Birmingham, 1968.Phys., 1965, 42, 3178.@ E. W. Hughes, J . Amer. Chern. SOC., 1941, 63, 1737
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