摘要:

Woodward�}Pre�Ê vost Reaction on Diosgenin and its Hydroxy Analogue Characterisation and Possible Mechanism for the Formation of Unusual Products Rita Katoch M. H. A. Baig and G. K. Trivedi* Department of Chemistry Indian Institute of Technology Mumbai-400076 India Woodward�}Pre�Ê vost reaction on diosgenin and its 4 -hydroxy derivative yielded polyhydroxy steroids 6�}8 and rearranged diosphenol 9 and aldehyde 10; a plausible mechanism involved in their formation is described. The synthesis and stereochemical studies of polyhydroxy sterols particularly those found in marine species such as sponges coelenterates molluscs and echinoderms,2 has been a challenging subject for synthetic chemists.7,23 Seeking to prepare the 3,4,5,6-tetrahydroxy derivative of diosgenin an important steroid drug precursor as a model intermediate to potential biologically active compounds we opted for the reaction of steroids with iodine silver acetate and wet acetic acid10 during our synthetic e€orts towards the hydroxylation of D5,6 steroids under mild conditions.The preparation of the tetrahydroxy derivative would be relatively easy since after the introduction of the cis dihydroxy groups on the D5,6-3-hydroxy steroids the additional hydroxy group could be introduced en-route via 4-acetoxy derivatives.11 Woodward-PreA vost reaction on diosgenin and its 4b- hydroxy derivative yielded unusual and unexpected poly- hydroxy steroids (Schemes 1 and 2). While the former gave a mixture of (25R)-spirost-4-en-3b,6a-diol-6-acetate (5 29.4%) (25R)-spirostan-3b,5a,6a-triol-6-acetate (6 25.2%) and (25R)-spirost-5-en-3b-ol-3-acetate (7 7.6%) the latter yielded (25R)-spirostan-3b,4b,5b,6b-tetrol-6-acetate (8 50%) (25R)-3-hydroxyspirost-2,5-dien-4-one (9 15%) and (25R)-3- (formyl)-A-norspirost-2,5-diene (10 5%).The formation of 5 and 6 can be rationalized through two competitive pathways. The initial attack on the double bond of 3 by I+ from IOAc results in b-iodonium ion which undergoes E2 elimination of iodine at C-5 with subsequent loss of 4a-hydrogen resulting in the formation of C-4�}C-5 double bond. The alternative route involves a-attack of OAc- on the iodonium intermediate which generates 5b- iodo-6a-acetoxy derivative in which owing to the loss of planarity the 4a-proton cannot participate in the replace- ment of the iodo group. Consequently the acetyl carbonyl group attacks from the alpha side to replace the iodo group and under the controlling in�Puence of water the corre- sponding cis-orthoacetate is formed which opens up regio- selectively to give 6.The yields indicate almost equal probability of the two pathways. In the absence of precedent literature it was dicult to anticipate the behaviour of a cyclic trisubstituted double bond having a participating allylic hydroxy group. The for- mation of these compounds can be rationalised by invoking the attack of IOAc on both sides of the oleRn. The a-face attack leads to the formation of the iodonium intermediate I. The opening of this cyclic intermediate leads to the for- mation of II. The acetyl carbonyl of II attacks from the b side to replace the iodo group and under the controlling in�Puence of water cis-orthoacetate III is formed which opens up regioselectively to give the major compound 8 J.Chem. Research (S) 1998 524�}525 J. Chem. Research (M) 1998 2401�}2419 Scheme 1 Woodward�}Pre�Ê vost reaction on diosgenin Scheme 2 Woodward�}Pre�Ê vost reaction on 4 -hydroxydiosgenin *To receive any correspondence. 524 J. CHEM. RESEARCH (S) 1998 (Fig. 3). Simultaneously the cyclic intermediate I' obtained from b-face attack on the ole®n could adopt either of the two pathways leading to compounds 9 and 10 (Fig. 4). Opening of the iodonium ion ring in I' followed by a 1,2- hydride shift gives a-ketol II' which undergoes silver ion assisted dehydroiodination to gve the a,b-unsaturated ketol III'. Ketol III' is converted to an oxidised diketo product V0 via a hypoiodite intermediate IV0.The intermediate V0 is then tautomerised to the observed diosphenol 9. Ketol III' also transforms through semi-benzylic rearrangement to the a-hydroxy aldehyde V' under the employed reaction conditions. Finally compound V' undergoes dehydration to give the rearranged product 10. Techniques used IR UV±VIS 1H and 13C NMR,MS Table 1 13C NMR chemical shifts of compounds 3 5 6 and 7 Table 2 13C NMR chemical shifts of compounds 4 8 9 and 10 Figures 4 References 23 Received 28th May 1998; Accepted 28th May 1998 Paper E/8/04016D References cited in this synopsis 2 S. Malik I. L. Stoilov and C. Djerassi Tetrahedron Lett. 1988 29 4081; J.-H. Sheu and T.-H. Yeh J. Chin. Chem. Soc. 1991 38 397; M. B. Ksebati and F. J. Schmitz Steroids 1984 43 639; M. Koboyashi T. Hayashi F. Nakajima and H. Mitsichashi Steroids 1979 34 285; B. Trush C. Hootele M. Kaisin D. Losman and R. Karlsson Steroids 1976 27 137. 7 J. M. Moldowan B. M. Tursch and C. Djerassi Steroids 1974 24 387; Y. Yamanda S. Suzuki K. Iguchi H. Kikuchi Y. Tsukilani H. Horia and H. Nakanishi Chem. Pharm. Bull. 1980 28 473; Jyh-Horng Sheu and Tsuey-Hue Yeh J. Chin. Chem. Soc. 1991 38 397. 10 B. Woodward and F. V. Brutcher Jr J. Am. Chem. Soc. 1958 80 209. 11 S. Korde M. H. A. Baig U. R. Desai and G. K. Trivedi Steroids 1996 61 290. 23 A. M. Brodie J. Steroid Biochem. Mol. Biol. 1994 49 281. Fig. 3 Plausible meachism towards formation of compound 8 Fig. 4 Mechanism involved in the formation of compounds 9 and 10 J.

ISSN:0308-2342    

DOI:10.1039/a804016h

出版商:RSC    

年代:1998

数据来源: RSC