/ August
16, I978
b~~.,si
carbon
6MeqSi
42.37 42.29 39.83 37.30 36.51 35.49 34.05 31.94 31.64
25 16 23 15 26, 27 II 19 21 18
30.43 28.14 26.92 24.28 21.65 21.11 19.38 18.69 1 1.87
Journal of the American Chemical Society / 100:17
5574
24-Ethyl-A~J~28~~28-cholestatrien-3/3-ola Naturally Occurring Allenic Marine Sterol' Sir: Marine sterols are characterized by unusual structural features in their side chains2 such as c y ~ l o p r o p a n e ,cyclo~,~ p r ~ p e n e and , ~ acetylene6 groupings. W e now report the first encounter of a naturally occurring sterol possessing an allenic side chain. Several years ago Erdman and Scheuer' examined the sterol composition of Callyspongia diffusa and identified nine known sterols, the principal among them being isofucosterol (1). Utilizing our recently described8 separation and analysis methods for detecting trace sterols we reinvestigated the sterol mixture of this sponge and isolated, in addition to the described sterols, 24-ketocholesterol (2)-a possible degraR
HO
2R=
...+ I
N
II
3, R =
...A I
N
4,
R=
I
-..A
Table I. I3CChemical Shifts (CDCI3) of cholestatrien-3B-0113)
carbon
he.,si
28 5 6 24 29 3 14 17 9
204.82 140.80 121.62 110.07 76.53 71.72 56.79 56.16 50.19
carbon 4 13 12 1 10
20 22 7, 8 2
position of the allene system can be derived from the mass spectrum; a typicalI4 McLafferty rearrangement to the central allene carbon yields an m/e 3 14 fragment which requires the presence of a A24(28),28-dienestructure. The 36-hydroxyA5-steroid nucleus is confirmed by the 'H and I3C N M R spectra (Table I). Thus all spectral data of this new marine sterol are in perfect agreement with structure 3. Final proof came from the catalytic hydrogenation of 3 with Pt02, which led to a mixture of C-24 epimeric sitosterols ( 5 ) . This first isolation of a steroidal allene is of obvious biogenetic interest since Minale and collaboratorsl5 recently showed that isofucosterol(1) is a biosynthetic precursor of the steroidal cyclopropene calysterol. It is conceivable that isofucosterol, which is a major sterol of Callyspongia diffusa,7 similarly is a precursor of 24-ethyl-A5,24(28),28-cholestatrien36-01 (3), but labeling experiments would have to be performed to establish this point. Even more interesting is the fact that our allene 3 had actually been synthesized by Ikekawa et a1.I6 in the course of a synthetic program looking for possible inhibitors of sterol biosynthesis. The synthetic allene 3 was found by them to be a specific inhibitor in the silkworm Bombyx mori in the transformation of sitosterol to fucosterol. It remains to be seen whether our isolation of this allene in nature indicates a specific biological role and what this role is in the marine environment.
I
Acknowledgment. We acknowledge financial support from the National Institutes of Health (Grants GM-06840 and AM-04257) and use of a 360-MHz N M R spectrometer made possible by grants from the National Science Foundation (GP-23633) and the N I H (RR0711).
5, R -
References and Notes dation product of isofucosterol (1)-and a new sterol (mp Part 7 of the Stanford series, "Minor and Trace Sterols in Marine Inverte1 13-1 14 "C) shown to be 24-ethyl-A5,24(28)~28-cholestatrien- (1) brates"; for part 6 see ref 2. (2) For leading references, see R. M. K. Carlson, S. Popov, I. Massey, C. 36-01 (3). Delseth, E. Ayanoglu. T. H. Varkony, and C. Djerassi, Bioorg. Chem.. in The mass spectrum of 3 exhibits a molecular ion of 410 press. (410.3516, calcd for C29H46O 410.35485) which indicates (3) R. L. Hale, J. Leciercq, B. Tursch, C. Djerassi, R. A. Gross, A. J. Weinheimer, R. Gupta, and P. J. Scheuer, J. Am. Chem. Soc.,92,2179 (1970: N. C. Ling, three degrees of unsaturation, assuming a n intact steroid nuR. L. Hale, and C. Djerassi, ibid., 92, 5281 (1970). cleus. The peaks at m/e 27 l , 28 l , 299, and 3 14 are typical9 for (4) F. J. Schrnitz and T. Pattabhiraman, J. Am. Chem. SOC., 92, 6073 (1970). an unsaturated side chain such as 24-methylenecholesterol (4). (5) E. Fattorusso, S.Magno, L. Mayol, C. Santacroce, and D. Sica, Tetrahedron. Together with the nuclear fragment ions at m/e 213, 229, and 31, 1715 (1975). 255, they clearly indicate that the second unsaturation must (6) E. Steiner, C. Djerassi, E. Fattorusso, S.Magno, L. Mayoi. C. Santacroce, and D. Sica, Helv. Chim. Acta, 60, 475 (1977). also be in the side chain and that the third one is in the nucleus (7) T. R. Erdman and P. J. Scheuer, Lloydia. 38, 359 (1975). at A5 or A7. The 360-MHz 'H N M R spectrum shows only five (8) S. Popov, R. M. K. Carison, A. Wegrnann, and C. Djerassi, Steroids, 28, 699 (1976). methyl group signals (C-18,0.673; (2-19, 1.003; C-21,0.930 (9) S.G. Wyllie and C. Djerassi. J. Org. Chem., 33, 305 (1968). (d); C-26,27, 1.010 ppm (d)),Io thus ruling out methyl groups (10) I. Rubenstein, L. J. Goad, A. D. H. Clague, andL. J. Mulheirn, phytochemistry, other than those present in cholesterol. A pseudoquartet (2 H , 15, 195 (197.6). (1 1) L. M. Jackman and S.Sternhell, "Application of Nuclear Magnetic Reso3 Hz) a t 4.68 ppm is typical' for a terminal methylene group, nance Spectroscopy in Organic Chemistry", 2nd ed, Pergamon Press, New and a double resonance experiment showed that these protons York, N.Y., 1969, pp 184-192. couple with the (2-25 hydrogen. The 13C N M R spectrum (12) J. W. Blunt and J. B. Stothers, Org. Magn. ReSon., 9, 439 (1977). (13) J. K. Crandall and S.A. Sojka, J. Am. Chem. Soc., 94, 5084 (1972). (Table I) displays, beside the signals corresponding to those (14) J. R. Wiersig, A. N. H. Yeo, and C. Djerassi. J. Am. Chem. Soc.. 99, 532 of cholesterol,12 three distinct signals a t 204.3, 110.1, and 76.5 (1977). (15) L. Minaie, R. Riccio, 0.Scalona, G. Sodano, E. Fattorusso, S.Magno, L. ppm (triplet in off-resonance experiment), which clearly inMayoi, and C. Santacroce, Experientia, 33, 1550 (1977). dicate a terminal allenic structure.13 This is confirmed by the (16) M. Morisaki, N. Awata, Y. Fujimoto, and N. Ikekawa, J. Chem. SOC.,Perkin characteristic allene infrared absorption a t 1950 cm-l. The Trans. 7, 2302 (1975); N. Awata, M. Morisaki, Y. Fujimoto, and N. Ikekawa. 0002-7863/78/1500-5574$01 . O O / O
0 1978 American Chemical Society
5515
Communications to the Editor J. Insect. Physiol.. 22, 403 (1976). Direct comparison of our material with a synthetic specimen provided by Dr. lkekawa established the identity. Varian Associates, Palo Alto, Calif. NIH Postdoctoral Fellow, 1971-1973.
Norbert Theobald, J. N. Shoolery,17 Carl Djerassi* Department of Chemistry, Stanford University Stanford, California 94305 Timothy R. Erdman,l* Paul J. Scheuer Department of Chemistry, University of Hawaii Honolulu, Hawaii 96822 Received May 1, 1978
Chiral Aggregation Phenomena. 1. Acid Dependent Chiral Recognition in a Monolayer
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