Tylosin synthesis

Matsubara, H., Inokoshi, J., Nakagawa, A., Tanaka, H., and Omura, S. (1983). Chemical modification of tylosin Synthesis of amino derivatives at C-20 position of tylosin and demycarosyl tylosin. J. Antibiot. 36,1713-1721. 

Mallams, A. K., and Rossman, R. R. (1989). Semisynthetic macrolide antibacterials derived tylosin. Synthesis of 23-O-demycinosyl tylosin and related compounds. J. Chem. Soc. Perkin Trans. /, 775-785. 

Tatsuta s tylosin synthesis is based on the coupling of the Ci-Cjo (180) and C11-C15 (182) segments derived from o-glucose, and on the stereo- and regio-... 

Tungsten, tricarbonyleyelopentadienylhydrido-reaction with ynamines, 1, 666 Turpin reaction, 3, 1033 Tylophorine occurrence, 4, 478 synthesis, 4, 472, 475 Tylosin... 

Scheme 5. Ketophosphonate-aldehyde condensation in the total synthesis of a tylosin system.

It has been demonstrated by Pancrazi, Ardisson and coworkers that an efficient kinetic resolution takes place when an excess (2 equivalents) of the racemic titanated alkenyl carbamate rac-334a (R = Me) is allowed to react with the enantiopure )-hydroxyaldehyde 341 or alternatively the corresponding y-lactol 340, since the mismatched pair contributes to a lower extent to the product ratio (equation 91) . Under best conditions, the ratio of the enantiomerically pure diastereomers 3,4-anti-4,5-syn (342) and 3,4-anti-4,5-anti (343) is close to 14 1. Surprisingly, approximately 9% of the iyw,iyw-diastereomer 344 resulted when the starting (ii)-crotyl carbamate was contaminated by the (Z)-isomer. The reasons which apply here are unknown. Extra base has to be used in order to neutrafize the free hydroxy group. The pure awft, awfi-product 345 was obtained with 85% yield from the reaction of the (W-oxy-substituted titanate rac-334b and lactol 340. 345 is an intermediate in the asymmetric synthesis of tylosine . ... 

M Tsuchiya, M Hamada, T Takeuchi, H Umezawa, K Yamamoto, H Tanaka, K Kiyoshima, S Mori, R Okamato. Studies of tylosin derivatives effective against macrolide-resistant strains synthesis and structure-activity relations. J Antibiot 35 661-672, 1982. 

Counter, F.T., Felty-Duckworth, A. M., Pekarek, R. S., Synthesis and evaluation of tylosin-rdated macrolides modified at the aldehyde function a new series of orally effective antibiotics. J. Med. Chem. 

The aldol reaction illustrated in eq 2 has been applied to the targeted synthesis of a number of complex molecules including Tylosin, Hapalosin, the antibiotic Sinefungin, and the HIV protease Saquinavir inhibitor. Oxazolidinone-type chiral auxiliaries derived from 1 have also been employed for the control of Diels-Alder reactions of attached acryloyl or crotonyl groups. ... 

Diisopinocampheylborane is not an effective asymmetric hy-droborating agent for 2-substituted 1-alkenes. High selectivities have, however, been achieved where one of the substituents is very bulky. This aspect has been elegantly demonstrated by the synthesis of both enantiomers of a precursor of tylonolide, the aglycone of tylosin, which is one of the members of the polyoxomacrolide antibiotics. In both cases the isomeric ratio was at least 50 1 (eqs eq 8 and eq 9). ... 

The improved in vitro spectrum, in vivo efficacy, and pharmacokinetics of certain esters of leucomycin-related macrolides logically led to the synthesis of analogous esters of tylosin. 3- and 4"-0-acyl derivatives were initially prepared by bioconversions with Streptomyces thermotolerans, a producer of carbomycin [76], From this small group, 3-0-acetyl-4"-0-isovalerylty-losin (AlV-tylosin) (14) Figure 5.6) was chosen for further study because of its activity against some tylosin-resistant organisms and its improved oral therapeutic and pharmacokinetic effects [61, 77], AlV-tylosin has now been commercially developed as a new veterinary antibiotic. 

Other reductive aminations of tylosin-related macrolides have been reported, including the synthesis of dimeric moieties which retain antibacterial activity [92,93]. Other modifications of the aldehyde group include a variety of hydrazone derivatives, reduction products, and C-alkylated analogues [83, 94]. 

Furthermore, esters of tylosin such as AIV (14) inhibited protein synthesis and bound to tylosin-resistant ribosomes [77], These results illustrate the dynamics of microbial resistance as antibiotics are developed to combat microorganisms which are continually evolving and acquiring new means of blocking the actions of antibiotics. 

Piletsky, S. Piletska, E.V. Karim, K. Foster, G. Legge, C. Turner, A. P. F., Custom synthesis of molecular imprinted polymers for biotechnological application Preparation of a polymer selective for tylosin, Anal. Chim. Acta. 2004, 504, 123-130... 

Section 2 deals with the synthesis of the more familiar biologically active maerolides, including the erythronolides, tylosin, and the leucomycin-carbomycin group. These compounds, many of which have important medicinal... 

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