An asymmetric synthesis of the macrolide antibiotic (-)-A26771B (1) has been developed wherein the stereochemistries at its C-5 and C-15 centres were installed using an (R)-BINOL-catalyzed allylation and a lipase-catalyzed acylation respectively. Acrylation at the C-15 centre under Mitsunobu conditions followed by a ring closing metathesis provided the macrocylic skeleton, which was suitably functionalized to obtain (-)-1. The biological assay of the antibiotic and two of its precursors suggested that presence of the γ-oxo moiety and the succinate function in (-)-1 were detrimental to its antibacterial activity.
(a) ÕmuraS. (1984) In Macrolide Antibiotics. Chemistry, Biology and Practice.ÕmuraS. (Ed). Academic Press, Orlando, pp. 509–552. (b) Tadashi N. (2002) Macrolide Antibiotics: Chemistry, Biology and Practice. (2nded). OmuraS. (Ed). Academic Press: SanDiego, pp. 181-284.
2.
MichelK.H., DemarcoP.V., NagarajanR. (1977) The isolation and structure elucidation of macrocyclic lactone antibiotic, A26771B. Journal of Antibiotics, 30, 571–575.
3.
(a) HaseT.A., NylundE.L. (1979) Synthesis of the macrolide antibiotic A26771B methyl ester. Tetrahedron Letters, 20, 2633–2636; (b) Asaoka M, Yanagida N, Takei H. (1980) Total synthesis of the macrolide antibiotic (±)-A26771B. Tetrahedron Letters, 21, 4611-4614; (c) Asaoka M, Abe M, Mukuta T, Takei H. (1982) Synthesis of macrocyclic lactones applying intramolecular 1,3-dipolar cycloaddition: Synthesis of (±)-A26771B. Chemistry Letters, 215-218; (d) Trost BM, Brickner SJ. (1983) Palladium-assisted macrocyclization approach to cytochalasins: A synthesis of antibiotic A26771B. Journal of American Chemical Society, 105, 568-575; (e) Fujisawa T, Okada N, Takeuchi M, Sato T. (1983) A short-step synthesis of antibiotic A26771B utilizing the ring-opening reaction of β-ethynyl-β-propiolactone. Chemistry Letters, 1271-1272; (f) Bestmann HJ, Schobert R. (1985) Oxidation of α,β-unsaturated esters and lactones with selenium dioxide to γ-oxo or γ-hydroxy derivatives; Synthesis of (±)-A26771B and norpyrenophorin. Angewandte Chemie International Edition in English, 24, 791-792; (g) Bienz S, Hesse M. (1987) Synthesis of macrocyclic α,β-unsaturated γ-oxolactones by ring-enlargement reactions; a new path to the macrocyclic lactone antibiotic A26771B. Helvetica Chimica Acta, 70, 1333-1340; (h) Baldwin JE, Adlington RM, Ramcharitar SH. (1991) Intramolecular palladium-catalysed cross coupling; a route to γ-oxo-α,β-unsaturated macrocycles. Journal of Chemical Society Chemical Communications, 940-942
4.
(a) TatsutaK., AmemiyaY., KanemuraY, KinoshitaM. (1982) Total synthesis of a macrocyclic lactone antibiotic A26771B and its isomers using carbohydrates. Bulletin of Chemical Society Japan, 55, 3248–3253; (b) Quinkert G, KueberF, Knauf W, Wacker M, Koch U, Becker H, Nestler HP, Dürner G, Zimmermann G, Bats JW, Egert E. (1991) Synthesis of the macrolide antibiotic (-)-A2677IB using photolactonization as a key reaction and computer simulation as an effective aid in optimization. Helvetica Chimica Acta, 74, 1853-1923; (c) Sinha SC, Sinha-Bagchi A, Keinan E. (1993) A general approach to enantiomerically pure methylcarbinols. Asymmetric synthesis of antibiotic (-)-A26771B and the WCR sex pheromone. Journal of Organic Chemistry, 58, 7789-7796; (d) Nagarajan M. (1999) Boc2O mediated macrolactonisation: Formal chemoenzymatic synthesis of macrolide antibiotic (-) A26771B. Tetrahedron Letters, 40, 1207-1210; (e) Kobayashi Y, Okui H. (2000) An efficient synthesis of antibiotic (-)-A26771B. Journal of Organic Chemistry, 65, 612-615; (f) LeeW, Shin HJ, Chang S. (2001)A rapid formal synthesis of the macrolide (-)-A26771B. Tetrahedron: Asymmetry, 12, 29-31; (g) Gebauer J, BlechertS. (2006) Synthesis of γ,δ-unsaturated-β-keto lactones via sequential cross metathesis-lactonization: A facile entry to macrolide antibiotic (-)-A26771B. Journal of Organic Chemistry, 71, 2021-2025; (h) Chatterjee S, Sharma A, Chattopadhyay S. (2014) Chemoenzymatic synthesis of the macrolide antibiotic (-)-A26771B. RSC Advances, 4, 42697-42705.
5.
GoswamiD., SurP., ChattopadhyayA., SharmaA., ChattopadhyayS. (2011) A novel asymmetric synthesis of the core octadienoic acid unit of cryptophycins from (R)-2,3-O-cyclohexylideneglyceraldehyde. Synthesis, 1626–1632, and the references cited therein.
6.
(a) TrnkaT.M., GrubbsR.H. (2001) The development of L2X2Ru≡CHR olefin metathesis catalysts: An organometallic success story. Account of Chemical Research, 34, 18–29; (b) Chatterjee AK, Choi TL, Sanders DP, Grubbs RH. (2003) A general model for selectivity in olefin cross metathesis. Journal of American Chemical Society, 125, 11360-11370.
7.
AraiK., RawlingsB.J., YoshizawaY, VederasJ.C. (1989) Biosyntheses of antibiotic A26771B by Penicilliumturbatum and dehydrocurvularin by Alternariacinerariae: Comparison of stereochemistry of polyketide and fatty acid enoyl thiol ester reductases. Journal of American Chemical Society, 111, 3391–3399.
