301153-91-3Relevant academic research and scientific papers
Novel chiral precursors of 6-s-cis locked 1α,25-dihydroxyvitamin D3 analogues through selective enzymatic acylation
Diaz, Monica,Ferrero, Miguel,Fernandez, Susana,Gotor, Vicente
, p. 539 - 546 (2007/10/03)
The syntheses of selectively modified chiral A-ring precursors for the preparation of 1α,25-dihydroxyvitamin D3 analogues by regioselective enzymatic acylation are described. Candida antarctica lipase B (CAL-B) catalyzes the acylation of 1α,25-dihydroxy-19-nor-previtamin D3 trans A-ring precursors 4 and 5 with high selectivity. The opposing regioselectivities observed for each pair of enantiomers is noteworthy: whereas CAL-B acylates the C-3 hydroxyl groups for derivatives of (3S,5R)-configuration, it catalyzes acylation at the C-5 hydroxyl group for substrates which possess (3R,5S)-stereochemistry. In relation to stereoisomer 4b, Chromobacterium viscosum lipase (CVL) showed opposite behavior to CAL-B, catalyzing acylation at the C-5 hydroxyl group with acceptable selectivity. In the enzymatic acylation of cis A-ring synthons 6 and 7, CVL gave total selectivity for acylation of the C-5 hydroxyl group of (3S,5S)-6 and the C-3 hydroxyl group of (3R,5R)-7. CAL-B also exhibits high selectivity towards the acylation of the C-3 hydroxyl in 19-nor-A-ring precursors with (3R,5R)-configuration.
6-s-cis locked analogues of the steroid hormone 1α,25-dihydroxyvitamin D3. Synthesis of novel A-ring stereoisomeric 1,25-dihydroxy-3-epi-19-nor-previtamin D3 derivatives
Diaz, Monica,Ferrero, Miguel,Fernandez, Susana,Gotor, Vicente
, p. 5647 - 5652 (2007/10/03)
Efficient syntheses of A-ring synthons 24 and 32 are described from hydroxy ester 16, which is easily available on a preparative scale from (-)-quinic acid. Key features of the syntheses were (a) the ability to selectively perform desilylations in the presence of p-nitrobenzoate esters and (b) the excellent yield and complete stereospecificity with which the configuration of alcohols 16, 18, and 26 could be inverted under Mitsunobu conditions. Thus, A-ring synthons 24 and 32 were both prepared in 35-38% yield (eight steps) from the common precursor 16. The coupling of A-ring synthons 24 and 32 with the appropriate CD-ring/side chain fragment 7 provides access to novel 6-s-cis locked analogues of steroid hormone 1α,25-dihydroxyvitamin D3: 1α,25-dihydroxy-3-epi-19-nor-previtamin D3 (37) and 1β,25-dihydroxy-3-epi-19-nor-previtamin D3 (38), which are unable to undergo rearrangement to the respective vitamin D form by virtue of the absence of the C-19 methyl group. Compounds 37 and 38 can be used as tools for studying the genomic and nongenomic mechanisms of action of the previtamin form of the hormone 1α,25-dihydroxyvitamin D3.
