113375-51-2Relevant academic research and scientific papers
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.
Functionalization of vitamin D metabolites at C-18 and application to the synthesis of 1 α, 18,25-trihydroxyvitamin D3 and 18,25-dihydroxyvitamin D3
Valles, Maria Jose,Castedo, Luis,Mourino, Antonio
, p. 1503 - 1506 (2007/10/02)
A general procedure for the introduction of a hydroxyl group at C-18 in several intermediates derived from the Inhoffen-Lythgoe diol is described for the first time. As an application, the syntheses of 1α, 18,25-trihydroxyvitamin D3 (2, dienyne
Palladium-catalysed coupling of vinyl triflates with enynes and its application to the synthesis of 1α,25-dihydroxyvitamin D3
Mascarenas,Sarandeses,Castedo,Mourino
, p. 3485 - 3498 (2007/10/02)
We describe a general approach, based on the palladium-catalysed coupling of enynes with vinyl triflates, for the construction of dienynes related to vitamin D metabolites and analogues. As an application of this method, an efficient convergent synthesis of 1α,25-dihydroxyvitamin D3 starting from the Inhoffen-Lythgoe diol (6a) and natural carvones has been carried out (11 steps, 28% overall yield from 6a). This strategy allows labelling of the side chain in the final steps of the synthesis.
Synthesis and Biological Activity of 9,11-Dehydrovitamin D3 analogues: Stereoselctive Preparation of 6β-Vitamin D Vinylallenes and a Concise Enynol Synthesis for Preparing the A-Ring
Okamura, William H.,Aurrecoechea, J. Miguel,Gibbs, Richard A.,Norman, Anthony W.
, p. 4072 - 4083 (2007/10/02)
The Δ9(11)-unsaturated vitamin D analogues 5a and 5b are of biochemical interest because they are incapable of tautomerizing via a sigmatropic hydrogen shift to a previtamin structure related to 3 and also becouse they possess a perturbed
AN IMPROVED SYNTHESIS OF 1α,25-DIHYDROXYVITAMIN D A SYNTHONS
Castedo, L.,Mascarenas, J. L.,Mourino, A.
, p. 2099 - 2102 (2007/10/02)
A new improved preparation of key intermediate (9b, 11) for the synthesis of 1α,25-dihydroxyvitamin D is described.
