Enzymatic Alkoxycarbonylation Research Articles

ChemInform Abstract: Vinyl Carbonates as Novel Alkoxycarbonylation Reagents in Enzymatic Synthesis of Carbonates.

Abstract Carbonates could be obtained by enzymatic alkoxycarbonylation from vinyl carbonates, which are easily prepared from vinylchloroformate. The reaction was catalyzed by Candida antartica lipases, SP 435 and SP 435 A. The method could be also used for the synthesis of carbamates. When racemic alcohols were used, lipase catalyzed their resolution, and chiral carbonates were obtained with different enantiomeric excesses depending upon the structure of the alcohol.

Chemoenzymatic synthesis and biological evaluation of C-3 carbamate analogues of 1α,25-dihydroxyvitamin D 3

The synthesis of new analogues of 1α,25-dihydroxyvitamin D 3 containing a carbamate function at the A-ring fragment has been described using the cross-coupling approach. The carbamate group was selectively introduced at the C-3 position by regioselective enzymatic alkoxycarbonylation of A-ring enyne 3 and subsequent treatment with ammonia, amines, amino alcohols, and amino acids. Biological studies to evaluate the potency of all five of these carbamate analogues were performed and demonstrated very low binding affinity for the vitamin D receptor compared with 1α,25-dihydroxyvitamin D 3. Moreover, all the carbamate analogues were less active than 1α,25-dihydroxyvitamin D 3 in inhibiting cell proliferation or stimulating cell differentiation. Of all the five analogues, the 3- O-carbamoyl-1α,25-(OH) 2-D 3 analogue 10a was the most potent one in vitro. However, all investigated carbamate analogues demonstrated lower calcemic effects in vivo than the parent compound.

First Regioselective Enzymatic Alkoxycarbonylation of Primary Amines. Synthesis of Novel 5′‐ and 3′‐Carbamates of Pyrimidine 3′,5′‐Diaminonucleoside Derivatives Including BVDU Analogues.

AbstractFor Abstract see ChemInform Abstract in Full Text.

First regioselective enzymatic alkoxycarbonylation of primary amines. Synthesis of novel 5'- and 3'-carbamates of pyrimidine 3',5'-diaminonucleoside derivatives including BVDU analogues.

The first regioselective enzymatic alkoxycarbonylation of primary amino groups has been achieved in pyrimidine 3',5'-diaminonucleoside derivatives. Thus, Candida antarctica lipase B (CAL-B) catalyzed this reaction with nonactivated homocarbonates allowing the selective synthesis of several N-5' carbamates, including (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) analogues, with moderate-high yields, whereas immobilized Pseudomonas cepacia lipase (PSL-C) afforded mixtures of alkoxycarbonylated regioisomers. To obtain N-3' carbamates selectively, a short and efficient chemoenzymatic route was used employing some of the N-5'-protected derivatives previously synthesized.

Enzymatic alkoxycarbonylation reactions on the intermediate in the synthesis of (−)-paroxetine, trans- N-benzyloxycarbonyl-4-(4′-fluorophenyl)-3-hydroxymethylpiperidine

Several enzymatic alkoxycarbonylation processes are evaluated for the resolution of trans- N-benzyloxycarbonyl-4-(4′-fluorophenyl)-3-hydroxymethylpiperidine, a chiral intermediate in the synthesis of (−)-paroxetine. Candida antarctica lipase B (CAL-B) catalyzes the enzymatic alkoxycarbonylation with diallylcarbonate with high enantioselectivity.

Enzymes in Organic Solvents: the Use of Lipases and (R)-Oxynitrilase for the Preparation of Products of Biological Interest

The use of enzymes in organic solvents has acquired a special relevance in organic synthesis, and lipases are the enzymes most commonly used in transesterication reactions. In the past few years, we have shown the utility of enzymatic aminolysis and ammonolysis reactions for the preparation of amides and for the resolution of esters and amines. The enzymatic alkoxycarbonylation reaction is of great utility in chemoselective reactions of natural products. Lipases, enzymes much less exploited in organic synthesis, have an increasing interest, especially the use of (R)-oxynitrilases for the synthesis of optically active cyanohydrins.

Enzymatic Amidation and Alkoxycarbonylation of Amines using Native and Immobilised Lipases with Different Origins: a Comparative Study

Enzymatic alkoxycarbonylation with vinyl carbonates and racemic amines can provide chiral carbamates. In the present paper, we have investigated the catalytic potential of some commercial lipases, with different origins. We have used the alkoxycarbonylation of ( R, S)-1-phenylethylamine, analysing the influence on the yield and enantioselectivity of some characteristics of the biocatalyts, such as the origin of the lipase and whether the lipase is immobilised or not. We have also investigated the influence on the yield of the chain length of the vinyl carbonate used as the acyl donor. Finally, we have probed this reaction, under the same conditions, with the chiral amines substituted in the aromatic ring, using p-chloro and p-methoxy-1-phenylethylamine and butyl vinyl carbonate.

1α,25-Dihydroxyvitamin D3 A-Ring Precursors: Studies on Regioselective Enzymatic Alkoxycarbonylation Reactions of Their Stereoisomers. Chemoenzymatic Synthesis of A-Ring Synthon Carbamate Derivatives, Including Carbazates and Polyamino Carbamates

The stereoisomers of 1α,25-dihydroxyvitamin D3 A-ring synthon 3a, named 3b−d, were subjected to a very comprehensive regioselective enzymatic study with Candida antarctica lipase (CAL). From this, it emerged that 3b, the enantiomer of the natural A-ring synthon, was a very good substrate for CAL in toluene, dioxane, or THF, showing in all cases conversions close to 100% and regioselectivities between 95% and 99% toward the C-5-(S) hydroxyl group. The best results for the regioselective enzymatic transformation of stereoisomer 3c were achieved with toluene at 30 °C or with THF at 60 °C. The regioselectivity displayed a preference toward the C-5-(S) hydroxyl group. The 1:10 ratio (3c:4) was mandatory so as to obtain an acceptable degree of conversion (in dioxane or THF). The A-ring synthon 3d has a surprising conduct, suffering C-5-(R) enzymatic alkoxycarbonylation, whereas in the acylation process with Chromobacterium viscosum lipase, it showed behavior opposite to that observed for 3a−c. In addition to th...

Chemoenzymatic Synthesis of Novel 3‘- and 5‘-Carbazoyl Nucleoside Derivatives. Regioselective Preparation of 3‘- and 5‘-Alkylidencarbazoyl Nucleosides

A chemoenzymatic procedure is described for the synthesis of 3‘- and 5‘-carbazoyl nucleoside derivatives 12a,b, 13a,b, 14b,c, and 30b, and these are prepared for the first time. This process involves the regioselective enzymatic alkoxycarbonylation of nucleosides and the subsequent transformation with hydrazine into novel carbazoyl nucleoside derivatives. Taking into account previously reported data (relative to nucleoside, hydrazone, carbazate, and aryloxyphenoxypropionate derivatives), 3‘-alkylidencarbazoyl 2‘-deoxynucleosides 15a,b−18a,b, 5‘-alkylidencarbazoyl 2‘-deoxynucleosides 19a,b−22a,b, 5‘-alkylidencarbazoyl ribonucleosides of uridine 23c−26c, and 5‘-alkylidencarbazoyl-2‘,3‘-isopropylideneadenosine 31b−34b emerge as interesting targets since they combine structural features found in both therapeutic nucleoside derivatives and fungicide/herbicide nucleoside analogues.

Selective Alkoxycarbonylation of A-Ring Precursors of Vitamin D Using Enzymes in Organic Solvents. Chemoenzymatic Synthesis of 1alpha,25-Dihydroxyvitamin D(3) C-5 A-Ring Carbamate Derivatives(1).

A-Ring modification of 1alpha,25-dihydroxyvitamin D(3) [2, 1alpha,25-(OH)(2)-D(3)] is an important area of analog studies to investigate biological activity of vitamin D-related structures. An efficient synthesis of 1alpha,25-(OH)(2)-D(3) C-5 A-ring carbamate derivatives 19 and amino acid derivatives 21 was developed by applying a two-step chemoenzymatic strategy, involving the enzymatic synthesis of carbonates followed by reaction with amino derivatives. Accordingly, we began the studies of enzymatic alkoxycarbonylation of 1alpha,25-(OH)(2)-D(3) A-ring precursor 7. Candida antarctica lipase (CAL) was found to be the best catalyst in toluene. Regioselective alkoxycarbonylation occurred only at the C-5-(R) hydroxyl group. Good to excellent yields were achieved by chemical reaction of these carbonates with amino derivatives. The procedure provided convenient synthesis of carbamates 19 and 21 under mild reaction conditions.

Enzymatic Regioselective Alkoxycarbonylation of Nucleosides and Its Utility in Nucleoside Derivative Synthesis

he regioselective enzymatic alkoxycarbonylation of nucleosides is described for α-, xylo-, anhydro-, and arabino-nucleosides to obtain Cbz-derivatives. The utility of these compounds and of the related vinyl carbonates of 2‘-deoxynucleosides is shown by the synthesis of 3‘-O-acetates of α-and xylo-thymidine and the synthesis of some nucleoside carbamates, respectively.

Chiral carbamates through an enzymatic alkoxycarbonylation reaction.

Chiral carbamates could be obtained by enzymatic alkoxycarbonylation with vinyl carbonates and racemic amines using Candida antarctica lipase. The enantioselectivity achieved depended on the substrate nature and the solvent.

Enzymatic regioselective alkoxycarbonylation of hexoses and pentoses with carbonate oxime esters

Hexoses and pentoses have been alkoxycarbonylated with different preparations of Candida antarctica lipase, using acetone O-(alkoxycarbonyl)oximes. A wide variety of alkoxycarbonyl groups are introduced in an easy manner at the primary hydroxy group of several pentoses and hexoses. Of especial importance are the introduction of allyloxy- and benzyloxy-carbonyl groups.

Lipase-mediated alkoxycarbonylation of nucleosides with oxime carbonates.

Abstract 5′-O-carbonates of ribonucleosides and 2′-deoxyribonucleosides could be obtained by enzymatic alkoxycarbonylation with SP 435 lipase (from Candida antarctica ) and oxime carbonates, which are easily prepared from chloroformates. Ribonucleosides gave as result two kind of 5′-O-carbonates depending on whether alkoxy or acetone oxime moiety acted as the leaving group. In the case of 2′-deoxynucleosides, the leaving group was always the acetonoxime moiety, giving rise to regioselective formation of the corresponding 5′-O-alkyl carbonates, together with small amounts of 3′-O-regiosiomer and diacylated compounds.

Vinyl carbonates as novel alkoxycarbonylation reagents in enzymatic synthesis of carbonates.

Carbonates could be obtained by enzymatic alkoxycarbonylation from vinyl carbonates, which are easily prepared from vinylchloroformate. The reaction was catalyzed by Candida antartica lipases, SP 435 and SP 435 A. The method could be also used for the synthesis of carbamates. When racemic alcohols were used, lipase catalyzed their resolution, and chiral carbonates were obtained with different enantiomeric excesses depending upon the structure of the alcohol.