Efficiency, chemoenzymatic synthesis

H. Hellmuth, L. Hillringhaus, S. Hobbel, S. Kralj, L. Dijkhuizen, and J. Seibel, Highly efficient chemoenzymatic synthesis of novel branched thiooligosacchar-ides by substrate direction with glucansucrases, Chembiochem, 8 (2007) 273-276. 

Hu S, Kelly S, Lee S, Tao J, Flahive E (2006) Efficient chemoenzymatic synthesis of Pelitrexol via enzymatic differentiation of a remote stereocenter. Org Lett 8 1653-1655... 

A very short and efficient chemoenzymatic synthesis of (—)-ephedrine can be achieved by a decarboxylase-mediated reaction of benzaldehyde with pyruvate... 

Ema T, Ide S et al (2008) Highly efficient chemoenzymatic synthesis of methyl (R)-o-chloromandelate, a key intermediate for clopidogrel, via asymmetric reduction with recombinant Escherichia coli. Adv Synth Catal 350 2039-2044... 

Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural a-2,6-linked sialosides a P. damsela a-2,6-sialyltransferase with extremely flexible donor-substrate 26. 

Brew K, Wang PG. Highly efficient chemoenzymatic synthesis of a-Galactosyl epitopes with arecombinant a(l—>3)-galactosyl- 91. 

While the thiazole and pyrimidine heterocycles of thiamin can be readily synthesized chemically, the thiazole/ pyrimidine coupling and the final pyrophosphorylation are difficult reactions. In contrast, the enzymatic syntheses of the thiazole and the pyrimidine are complex, but the coupling and phosphorylation chemistry is straightforward. This synthetic/biosynthetic complementarity has been utilized in the development of an efficient chemoenzymatic synthesis of thiamin pyrophosphate (Figure 13). This route has been used for the preparation of isotopically labeled thiamin pyrophosphate to characterize the thiamin radical found in pyruvateferredoxin oxidoreductase and is the preferred method to synthesize isotopically labeled forms of thiamin pyrophosphate. 

Zhang J, Kowal P, Fang J, Andreana P, Wang PG. Efficient chemoenzymatic synthesis of globotriose and its derivatives with a recombinant a-(1 4)-galac-tosyltransferase. Carbohydr Res 2002 337 969-976. 

Hu S, Martinez C, Kline B, Yazbeck D, Tao J, Kucera D (2006) Efficient and scalable enzymatic process for the production of (2S)-4,4-difluoro-3,3-di-methyl-N-Boc-proline, a key intermediate in the synthesis of HIV protease inhibitors. Org Process Res Dev 10 650-654 Hu S, Kelly S, Lee S, Tao J, Elahive E (2006) Efficient chemoenzymatic synthesis of Pelitrexol via enzymatic differentiation of a remote stereocenter. Org Lett 8 1653-1655... 

X. (2011) Efficient chemoenzymatic synthesis of sialyl Tn-antigens and derivatives. Chem. Commun. (Cambridge. U.K.), 47, 8691 8693. 

Yu, H., Huang, S., Chokhawala, H., Sun, M., Zheng, H., and Chen, X., Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural a-2,6-linked sialosides A P. damsela a-2,6-sialyltransferase with extremely flexible donor-substrate specificity. Angew. Chem. Int. Ed. 2006,45 (24), 3938-3944. 

Bufuralol is a nonselective (3-adrenoreceptor blocking agent of comparable potency to propranolol. It has proven to be effective in treating hypertension and is a potent nonselective p-adrenergic receptor antagonist. Similarly to the method described earlier in Scheme 57.9, an efficient chemoenzymatic synthesis of (/ )-bufuralol has been reported involving a DKR of the chlorohydrin key intermediate rac-44 (Scheme 57.10). ... 

An efficient chemoenzymatic synthesis of both enantiomers 142 and 143 of an LTD4 antagonist have been prepared by lipase-catalyzed asymmetrical hydrolysis of prochiral and racemic dithioacetal esters 144 having up to five bonds between die prochiral/chiral center and the ester carbonyl group. The e.e. of 98% and reaction yield of 45% were obtained using lipase PS-30 (Fig. 51). LTD4 antagonists have potential for the dierapeutic treatment of asthma [251]. 

An efficient chemoenzymatic route for the synthesis of optically active substituted indolines has been recently developed (Scheme 7.27), and also the alkoxycarbonyla-tion process is more efficient than the acylation reaction. Different lipases have been tested in the alkoxycarbonylation of these secondary amines, GALA being found to be the best biocatalyst for 2-substituted-indolines, and CALB for 3-methylindoline. The combination of lipases with a variety of allyl carbonates and TBME as solvent has allowed the isolation of the carbamate and amine derivatives in a high level of enantiopurity [51]. 

The combined use of enzymatic and chemical methods under the so-called chemoenzymatic synthesis offers the flexibility of chemical synthesis and the high regioselectivity and stereoselectivity of enzyme-catalyzed reactions to achieve highly efficient synthesis of complex carbohydrates. Chemoenzymatic glycosylation is... 

Guanti, G., Banfi, L., Basso, A., Bevilacqua, E., Bondanza, L., and Riva, R. 2004. Efficient chemoenzymatic enantioselective synthesis of diacylglycerols (DAG). Tetrahedron Asymm., 15, 2889-2892. 

Wang, M.X., Deng, G., Wang, D.X., et al. 2005. Nitrile biotransformation for highly enantioselective synthesis of oxiranecarboxamides with tertiary and quaternary sterocenters efficient chemoenzymatic approaches to enantiopur a-methylated serine and isoserine derivatives. Journal of Organic Chemistry, 70 2439-44. 

Fumoto M, Hinou H, Matsushita T, Kurogochi M, Ohta T, Ito T, Yamada K, Takimoto A, Kondo H, Inazu T, Nishimura S. Molecular transporter between polymer platforms highly efficient chemoenzymatic glycopeptide synthesis by the combined use of solid-phase and water-soluble polymer supports. Angew. Chem. Int. Ed. Engl. 2005 44 2534-2537. 

As a part of ongoing efforts to synthesize a potent, orally active anti-platelet agent, xemilofiban 1 [1], development of an efficient chemoenzymatic process for 2, the chiral yS-amino acid ester synthon (Fig. 1) was proposed. The scheme emphasized the creation of the stereogenic center as the key step. In parallel with the enzymatic approach, chemical synthesis of the / -amino acid ester synthon emphasized formation of a chiral imine, nucleophilic addition of the Reformatsky reagent, and oxidative removal of the chiral auxiliary. This chapter describes a selective amida-tion/amide hydrolysis using the enzyme Penicillin G amidohydrolase from E. coli to synthesize (R)- and (S)-enantiomers of ethyl 3-amino-5-(trimethylsilyl)-4-pen-tynoate in an optically pure form. The design of the experimental approach was applied in order to optimize the critical reaction parameters to control the stereoselectivity of the enzyme Penicillin G amidohydrolase. 

Figure 4 (a) Representative examples to apply PikAIII and PikAIV in the preparation of natural and unnatural products through chemoenzymatic synthesis. PikAI 11 and PikAIV alone or their combination are capable of producing a diverse series of products. (b) Two reactions catalyzed by excised Pik TE domain. The excised TE domain efficiently catalyzes macrolactonization of NAC-hexaketide but produces the linear hydrolytic product when the substrate was modified with a hydroxyl group at the 07 position. 

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