Section 47
Chapter 46,790

New Synthetic Strategies to Vitamin D Analogues Modified at the Side Chain and D Ring. Synthesis of 1alpha,25-Dihydroxy-16-ene-vitamin D (3) and C-20 Analogues (1)

De Los Angeles Rey, M.ía.; Martínez-Pérez, J.é A.; Fernández-Gacio, A.; Halkes, K.; Fall, Y.; Granja, J.; Mouriño, A.

Journal of Organic Chemistry 64(9): 3196-3206


ISSN/ISBN: 1520-6904
PMID: 11674421
DOI: 10.1021/jo982393e
Accession: 046789544

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Two efficient synthetic routes to 1alpha,25-dihydroxy-16-ene-vitamin D(3) (4a) and their C-20 analogues (3 and 4) have been developed. Key features common to both routes A and B are the introduction of side chains functionalized at C20 (17, 21, 19, and 25). In route A the CD side chain fragments 5 and 6 are prepared by S(N)2' syn displacement of allylic carbamates 8 and 9 (X = OCONHPh) by Li(2)Cu(3)R(5). The triene unit is then constructed by assembling the latter fragments with the A-ring fragment using the Wittig-Horner method (average yield of vitamin D analogue 35%, 11-13 steps from ketone 11). In route B, the S(N)2' syn displacement of the carbamate moiety by Li(2)Cu(3)R(5) is carried out on intermediates 12 and 13, both of which bear the vitamin D triene unit (average yield of vitamin D analogue 27%, 13-15 steps from ketone 11). The latter route is particularly attractive as an approach to diverse C-20 vitamin D analogues for biological screening.

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