169437-97-2Relevant articles and documents
Regioselective enzymatic syntheses of C-3 and C-5 carbonate A-ring stereoisomeric precursors of vitamin D
Oves, Daniel,Gotor-Fernandez, Vicente,Fernandez, Susana,Ferrero, Miguel,Gotor, Vicente
, p. 2881 - 2887 (2007/10/03)
The synthesis of selectively modified A-ring precursors for the preparation of 1α,25-dihydroxyvitamin D3 analogues by enzymatic hydrolysis reaction of corresponding dicarbonates has been accomplished. Thus, Candida rugosa lipase (CRL) was found to hydrolyze with high selectivity the C-3 carbonate of stereoisomers 4a,b, and 4d, furnishing C-5 vinyloxycarbonates 5a,b, and 5d. On the other hand, Chromobacterium viscosum lipase exhibit opposite regioselectivity with cis enantiomers 4c and 4d, catalyzing hydrolysis at the C-5 carbonate for 4c and at C-3 position for 4d. In addition, CRL catalyzes the alkoxycarbonylation reaction at C-3 of diol 3d affording the monocarbonate complementary to the one obtained by the enzymatic hydrolysis process.
Synthesis of monoacyl A-ring precursors of 1α,25-dihydroxyvitamin D3 through selective enzymatic hydrolysis
Gotor-Fernandez, Vicente,Ferrero, Miguel,Fernandez, Susana,Gotor, Vicente
, p. 1266 - 1270 (2007/10/03)
An efficient synthesis of monoacylated 1α,25-dihydroxyvitamin D3 A-ring precursors 15, 16, 18, and 19 has been described through an enzymatic hydrolysis process. Candida antarctica A lipase (CAL-A) hydrolyzes the C-5 acetate ester in trans stereoisomers 9 and 13, with complete and high selectivity, respectively. In the case of cis isomers 11 and 14, Chromobacterium viscosum lipase (CVL) is the enzyme of choice, exhibiting opposite selectivity for these two enantiomers. This lipase selectively catalyzes the hydrolysis at the C-3 acetate in diester 11 and at C-5 position in diester 14. It is noteworthy that through a hydrolysis reaction CAL-A and CVL allow the synthesis of the four A-ring monoacetylated precursors of 1α,25-dihydroxyvitamin D3, precursors which are complementary to those obtained by the enzymatic acylation process. In addition, with excellent yield CVL selectively hydrolyzes the C-3 chloroacetate ester instead of the C-5 acetate in diester 22, a key intermediate in the synthesis of new A-ring modified 1α,25-dihydroxyvitamin D3 analogues.
Selective acylation of A-ring precursors of vitamin D using enzymes in organic solvents
Fernandez,Ferrero,Gotor,Okamura
, p. 6057 - 6061 (2007/10/03)
Whereas Chromobacterium viscosum lipase (CVL) catalyzes selectively the acylation of the C-5 hydroxyl of the three stereoisomeric vitamin D A-ring precursors 2a, 3a and 3b, only the C-3 hydroxyl of the fourth stereoisomer 2b is acylated under the same conditions in organic solvent. In a convenient application, the racemic vitamin D A-ring precursor 4, possessing only the C-5 hydroxyl, was resolved using suitable conditions identified from the studies of 2 and 3.
