169437-97-2

Upstream product

• 169305-41-3 (5R)-3-Ethynyl-5-hydroxy-2-methyl-2-cyclohexen-1-one 
• 405229-45-0 (3R,5R)-3,5-diacetoxy-1-ethynyl-2-methylcyclohex-1-ene 
• 350985-91-0 (3R,5R)-5-acetoxy-1-ethynyl-2-methyl-3-[(4-nitrophenyl)carbonyloxy]cyclohex-1-ene 
• 113375-51-2 (3S,5R)-1-ethynyl-3,5-dihydroxy-2-methylcyclohex-1-ene 
• 115540-15-3 (1S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene 
• 250590-31-9 (3R,5R)-1-ethynyl-2-methyl-3,5-bis[(vinyloxy)carbonyloxy]-1-cyclohexene 

Downstream Products

• 250590-28-4 (3R,5R)-1-ethynyl-3-hydroxy-2-methyl-5-[(vinyloxy)carbonyloxy]-1-cyclohexene 
• 797037-94-6 (3R,5R)-1-ethynyl-5-hydroxy-2-methyl-3-[(vinyloxy)carbonyloxy]-1-cyclohexene 
• 250590-31-9 (3R,5R)-1-ethynyl-2-methyl-3,5-bis[(vinyloxy)carbonyloxy]-1-cyclohexene 
• 405229-45-0 (3R,5R)-3,5-diacetoxy-1-ethynyl-2-methylcyclohex-1-ene 
• 405197-18-4 (3R,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene 

Relevant academic research and scientific papers

Regioselective enzymatic syntheses of C-3 and C-5 carbonate A-ring stereoisomeric precursors of vitamin D

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.

Efficient synthesis of novel 1α-amino and 3β-amino analogues of 1α,25-dihydroxyvitamin D3

Convenient synthetic routes to 1α-amino-25-hydroxyvitamin D3 (3) and 3β-amino-3-deoxy-1α,25-dihydroxyvitamin D3 (4), novel analogues of vitamin D3 bearing an amino group at the C-1 or C-3 position, have been developed starting from (S)-(+)-carvone. Construction of the A-ring fragments was accomplished by selective enzymatic hydrolysis of a diester intermediate and introduction of the amino group under Mitsunobu conditions.

Synthesis of monoacyl A-ring precursors of 1α,25-dihydroxyvitamin D3 through selective enzymatic hydrolysis

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.

CAL-B-catalyzed alkoxycarbonylation of A-ring stereoisomeric synthons of 1α,25-dihydroxyvitamin D3 and 1α,25-dihydroxy-19-nor-previtamin D3: A comparative study. First regioselective chemoenzymatic synthesis of 19-nor-A-ring carbonates

A comparative study of alkoxycarbonylation processes of both 19-nor-A-ring and A-ring stereoisomers of 1α,25-dihydroxyvitamin D3 analogues catalyzed by Candida antarctica lipase B (CAL-B) has been described. The presence of the methyl group in the A-ring at C-2, as in 3-6, has a determining role in the regioselectivity of the biocatalysis, mainly allowing the hydroxyl group at C-5 position to react. For the 19-nor-A-ring stereoisomers 7-10, which lack the C-2 methyl group, the configurations at C-3 and C-5 have a high influence in the selectivity exhibited by CAL-B. Thus, each couple of enantiomers showed opposing regioselectivities depending on the C-3 configuration. When C-3 possesses an (S)-configuration, enzymatic alkoxycarbonylations took place at the C-5-(R) or C-5-(S) hydroxyl groups. However, if the chiral centers at C-3 are (R), CAL-B alkoxycarbonylated the C-3-(R) hydroxyl group independently of the configuration at C-5. The corresponding carbonates are useful A-ring precursors of 1α,25-dihydroxyvitamin D3 analogues, selectively modified at the C-1 or C-3 positions. In addition, an improved synthesis of cis A-ring synthons 5 and 6 is described using a Mitsunobu methodology.

Selective acylation of A-ring precursors of vitamin D using enzymes in organic solvents

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.