Synthesis of macrolide antibiotics. 20. Synthesis of erythronolide A

A complete, stereocontrolled synthesis for erythronolide A was carried out by fusion of the (C⁹-C¹³)+(C⁷-C⁸)+(C¹-C⁶) fragments from levoglucosan in 61 steps with 0.28% total yield.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 195–199, January, 1990.     

Synthesis of macrolide antibiotics. 1. Synthesis of the C1-C6 segment of 14-membered macrolide antibiotics.

The C₁-C₆ segment of a number of 14-membered macrolide antibiotics have been synthesized started from levoglucosan.     

Synthesis of macrolide antibiotics. 22. Synthesis of the C8-C13 fragment of oleandonolide

The stereospecific synthesis of the C⁸-C¹³ fragment of oleandonolide was carried out in 15 steps with an overall yield of 4.48%.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2136–2142, September, 1991.     

Synthesis of macrolide antibiotics. 19. Synthesis of the C7-C13 fragment of erythronolide A

A stereocontrolled synthesis was carried out for the C⁷-C¹³ fragment of erythronolide A in 33 steps with an overall yield of 13% relative to starting levoglucosan.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 186–195, January, 1990.     

Synthesis of macrolide antibiotics Communication 4. Synthesis of the C11-C13 fragment of narbomycin

Conclusions The synthesis has been effected from 1,6-anhydro--D-glucopyranose (10 steps, overall yield 28.9%) of the C¹¹-C¹³ fragment of narbomycin, a polychiral 14-membered macrolide antiobiotic.For communication 3, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2572–2575, November, 1982.     

Synthesis of macrolide antibiotics 21. Retrosynthetic analysis of oleandonolide and macrolactonization of its seco-acid

A retrosynthetic scheme for preparing oleandonolide was examined, and the possibility of macrolactonization of the seco-acid of oleandonolide to a lactone was investigated.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2133–2136, September, 1991.     

Synthesis of macrolide antibiotics. 13. synthesis of certain derivatives of the seco-acid of erythronolide B

Conclusions The synthesis of 9-R-8-hydroxymethyl epi derivative of the seco acid 9-dihydroerythronolide B was carried out and its macrolactonization was studied.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 165–171, January, 1989.     

Synthesis of macrolide antibiotics. 18. Stereospecific building up of the carbon chain of erythronolide B

Conclusions A stereodirected synthesis of erythronolide B carbon chain was carried out starting from from levoglucosan.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 688–693, March, 1989.     

Synthesis of macrolide antibiotics. Communication 8. Synthesis of acyclic forms of C9-C13 fragment of erythronolide B

Conclusions A synthesis of three acyclic forms of the C⁹-C¹³ fragment of erythronolide B has been carried out.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1166–1172, May, 1985.     

Synthesis of macrolide antibiotics Communication 3. Synthesis of the C9-C13 fragments of oleandonolide and erythronolide B

Conclusions Using Cp₂Zr(H)Cl, 1,6-anhydro-2-desoxy-2-C-methyl-3-O-benzyl-4-methylene--D-xylohexapyranose has been reduced with a high degree of stereospecificity to 1,6-anhydro-2,4-didesoxy-2,4-di-C-methyl-3-Obenzyl--D-galactopyranose, which was then converted into the C⁹-C¹³ fragments of erythronolide Band oleandonolide.Short communication [1]; previous communication [2].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2568–2572, November, 1982.     

Synthesis of new 14-membered macrolide antibiotics via a novel ring contraction metathesis

[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.     

Determination of macrolide antibiotics by liquid chromatography

The liquid chromatographic separation of seven macrolides used in food producing animals in the European Union has been studied. Separation was performed by using an end-capped high-purity silica-based C₁₈ column and mobile phases consisting of phosphate buffer (pH 2.5)–acetonitrile mixtures. The effect of pH and acetonitrile percentage on the separation was examined. Two UV-based detection systems, wavelength programming and diode array, were assayed. Detection limits were in the range 6–33 μg l⁻¹ for spiramycin, tilmicosin, tylosin, kitasamicin and josamicin and about 400 μg l⁻¹ for erythromycin and oleandomycin. The suitability of the method for multiresidue determination of the five macrolides is demonstrated by the analysis of spiked samples of chicken muscle.     

Synthesis of macrolide antibiotics. 17. Synthesis of the C1-C10-fragment of erythronolides (A) and (B)

Conclusions A synthesis of the C¹-C¹⁰ fragment of erythronolides (A) and (B) with a reliably established configuration of the C³-C⁶ and C⁸ centers has been carried out.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 680–687, March, 1989.