Chemo-Enzymatic Synthesis

Taylor, S.J.C., Sutherland, A.G., Lee, C., Wisdom, R., Thomas, S., Roberts, S.M. and Evans, C., Chemoenzymatic synthesis of (—)-carhovir utilizing a whole cell catalysed resolution of 2-azabicyclo[2.2.1 ]hept-5-en-3-one. J. Chem. Soc. Chem. Commun., 1990, 1120-1121 Evans, C.T., Roberts, S.M., Shoheru, K.A. and Sutherland, A.G., Potential use of carbocyclic nucleosides for the treatment of AIDS chemo-enzymatic syntheses of the enantiomers of carbovir. J. Chem. Soc. Perkin Trans. 1,1992, 589-592. 

A. Naundorf and W. KlaHke, Substrate specificity of native dTDP-D-glucose-4,6-dehydratase chemo-enzymatic syntheses of artificial and naturally occurring deoxy sugar, Carbohydr. Res., 285 (1996) 141-150. 

Photoaffinity analogs of UDP-Xyl and UDP-GlcA have been chemo-enzymatically synthesized for a covalent derivatization and 32P-labeling of membrane-bound glycosyltransferases and nucleotide sugar metabolizing enzymes (Table 4) [322, 325, 359, 360],... 

Amino- and Imino-alditols - Reviews on the syntheses of azasugars (imi-noalditols) from non-carbohydrate sources on the syntheses of azasugars, sugar amidines and related structures as inhibitors of carbohydrate-processing enzymes on the syntheses of glycosidase inhibitors with reference to nag-statin and on the use of aldolases in the chemo-enzymatic syntheses of iminoalditols have appeared. 

The chemo-enzymatic syntheses (O Fig. 41.33) of the aromatic amino acids, 3,4-dihydroxy-L-phenylalanine (DOPA), L-tyrosine, L-tryptophan, 5-hydroxy-L-tryptophan (5-HTP), and analogues thereof, "C-labeled either in the carboxylic- or P-position (Bjurling and Langstrom 1989 Bjurling et al. 1990a, b Sasaki et al. 1999 Harada et al. 1999 Ikemoto et al. 1999) are other important achievements. 

Chemo-enzymatic syntheses of aliphatic amino acids by C-C bond formation... 

K. A. Shoberu, and A.G. Sutherland, Potential use of carbocyclic nucleosides for the treatment of AIDS chemo-enzymatic syntheses of the enantiomers of carbovir, J. Chem. Soc., Perkin Trans. 1 589 (1992). 

A dideoxygenated pentasaccharide, which was chemo-enzymatically synthesized by use of GnT II [106], and a di-O-methylated pentasaccharide were active as substrates for GnT III (E.C. 2.4.1.144) producing the expected hexasaccharide analogs [108, 109],... 

Khedri, Z., Muthana, M. M., Li, Y., Muthana, S. M., Yu, H., Cao, H., and Chen, X., Probe sialidase substrate specificity using chemo-enzymatically synthesized sialosides containing C9-modified sialic acid. Chem. Commun. 2012, 48 (27), 3357-3359. 

The reduction of a-hydroxynitriles to yield vicinal amino alcohols is conveniently accomplished with complex metal hydrides for example, lithium aluminum hydride or sodium borohydride [69]. However, it is still worth noting that a two-step chemo-enzymatic synthesis of (R)-2-amino-l-(2-furyl)ethanol for laboratory production was developed followed by successful up-scaling to kilogram scale using NaBH4/CF3COOH as reductant [70],... 

D Arrigo, P, Lattanzio, M., Fantoni, P. and Servi, S. (1998) Chemo-enzymatic synthesis of the active enantiomer of the anorressant 2-benzylmorpholine. Tetrahedron Asymmetry, 9, 4021 -026. 

Procedure 2 Chemo-enzymatic Synthesis of 5-Thio-D-xylulofuranose. Route A TK-catalysed Bond Formation... 

Zanini D, Roy R (1996) Chemo-enzymatic synthesis of multivalent N-acetyllactosamine compounds as dendritic sialyl LewisX precursors. Proceedings of the XVIlIth International Carbohydrate Symposium, Milan, Italy, Juli 21 -26, p 236 Pag6 D, Zanini, D, Roy R (1996) Bioorg Med Chem 4 1949 Roy R, Baek MG, Zanini D, (unpublished data)... 

To catalyze a protective step in a chemo-enzymatic synthesis of sugar derivatives or of more complex oligosaccharides. 

In other reports, the lipase-catalyzed acylation of benzylidene derivatives of sugars, useful intermediates in the synthesis of oligosaccharides, has been described [42]. For example, the esterification of 4,6-O-benzylidene-a-D-glucopy-ranoside (13) with vinyl acetate by action of Pseudomonas cepacia lipase gave quantitatively the 2-O-acetate 13a. [42b] As a third case, it deserves to be mentioned the extensive work of Russo and coworkers for the chemo-enzymatic synthesis of milk oligosaccharides [43]. 

More recently, the chemo-enzymatic synthesis of inulin-containing hydrogels was reported [54]. The key point was the solubility of inulin [a mixture of oligomers and polymers containing 2-60 (or more) 5-2,1 linked D-fructose molecules having a glucose unit as the initial residue] in dimethylformamide (DMF), a fact that allowed its esterification by action of a protease from Bacillus subtilis. 

S. L. Flitsch, H. L. Pinches, J. P. Taylor, and N. J. Turner, Chemo-enzymatic synthesis of a lipid-linked core trisaccharide of N-linked glycoproteins, J. Chem. Soc. Perkin Trans. 1 2081 (1992). 

Chi-Huey Wong (USA) Enzymatic and chemo-enzymatic synthesis of carbohydrates... 

S. Amann, G. Drager, C. Rupprath, A. Kirschning, and L. Elling, (Chemo)enzymatic synthesis of dTDP-activated 2,6-dideoxysugars as building blocks of polyketide antibiotics, Carbohydr. Res., 335 (2001) 23-32. 

Patel RN (2008) Chemo-enzymatic synthesis of pharmaceutical intermediates. Expert Opin Drug Discov 3 187-245... 

Keywords Alkaloids Chemo-enzymatic synthesis Enzymatic formation Generation of diversity Genetic approaches... 

Chemo-Enzymatic Synthesis of Monoterpenoid Indole Alkaloids. 78... 

Chemo-Enzymatic Synthesis of Other Alkaloids Selected Examples. 91... 

A retrosynthetic synthesis of (—)antirhine (Fig. 11) was performed through the monoacetate (1) and lactone (2) which was condensed with tryptamine. Product 3 was then finally converted, through a number of intermediates, to the tetracyclic (—)-antirhine, resulting in a remarkable overall yield of 13% (starting from the monoacetate 1), together with the 3-epimer (+)-antirhine at a yield of 6%. This strategy allowed the chemo-enzymatic synthesis of both (—) - and (+)-antirhines [82]. 

Fig. 10 Enzyme-catalysed formation of chiral monoacetate synthons from meso-diacetate or meso-diol for chemo-enzymatic synthesis of monoterpenoid indole alkaloids...

Fig. 12 First enantio-selective, chemo-enzymatic synthesis of the monoterpenoid indole alkaloid (-)-akagerine, member of the family of Strychnos alkaloids...

The total chemo-enzymatic synthesis of three of the (-l-)-montanine alkaloids, namely (+)-brunsvigine [138], (-l-)-nangustine [139] and (-l-)-montabuphine [140], has been reported in the last 3 years. These non-natural enantiomers have been prepared from monochiral 3-halo-m-1,2-dihydrocatechols precursors. A total of over 17-20 reaction steps are needed for their syntheses (Fig. 22). 

More effort was therefore invested in the application of synthetic methodologies for these alkaloids and some straightforward chemo-enzymatic approaches were recently developed [150]. An enzyme-catalysed aldol reaction was again a crucial step in that synthetic route and is strongly reminiscent of Wong s research strategy relating to the chemo-enzymatic synthesis of pyrrolizidines mentioned earlier. 

For the described approach, it is important to note that aldolases of different origin were tested and that, in contrast to L-rhamnulose-1-phosphate aldolase (RhuA), the D-fructose-1,6-biphosphate aldolase from rabbit muscle and L-fucu-lose-1-phosphate aldolase from E. coli were not active for DHAP/(R)-N- and (S)-iV-Cbz-prolinal condensation. Since RhuA accepts both, (S)-N- and (R)-N-Cbz prolinals, the chemo-enzymatic synthesis of both, hyacinthacines A and A2 isomers could be achieved. In conclusion, the origin and the particular enzyme itself... 

Figure 1 Chemo-enzymatic synthesis of an ECB antifungal agent.

The ability of the hyperthermophilic glycosynthases to promote the synthesis of oligosaccharides is a clear example of how the unique characteristics of stability to high temperatures and acidic pH of the glycosidases from hyperthermophilic archaea allows the development of a novel strategy for the chemo-enzymatic synthesis of oligosaccharides. 

Belokon YN, Blacker AJ, Clutterbuck LA, Hogg D, North M, Reeve C (2006) An asymmetric, chemo-enzymatic synthesis of O-acetylcyanohydrins. Eur J Org Chem 4609-4617... 

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