Enantioselective total synthesis of altohyrtin C (spongistatin 2)

• Published in: Tetrahedron Vol. 55; no. 29; pp. 8671 - 8726
• Main Authors: Evans, David A., Trotter, B.Wesley, Coleman, Paul J., Côté, Bernard, Dias, Luiz Carlos, Rajapakse, Hemaka A., Tyler, Andrew N.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 16.07.1999; Elsevier
• Subjects: aldol reactions; antitumour compounds; asymmetric synthesis; Chemistry; Chemistry, Organic; marine metabolites; Physical Sciences; Science & Technology; asymmetric synthesis; aldol reactions; marine metabolites; antitumour compounds; CHIRAL LEWIS-ACIDS; CONVENIENT SYNTHESIS; ASYMMETRIC-SYNTHESIS; DIELS-ALDER REACTIONS; SPONGE HYRTIOS-ALTUM; MARINE MACROLIDE SYNTHESIS; RELATIVE 1,2-ASYMMETRIC INDUCTION; D-GLYCOPYRANOSYL PHENYLSULFONES; ALDOL ADDITION-REACTIONS; STEREOCONTROLLED SYNTHESIS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(99)00438-X

The first total synthesis of a spongipyran macrolide, altohyrtin C, is described. The convergent synthesis strategy relies on a regioselective macrolactonization, a stereoselective Wittig coupling of the two major synthetic fragments, a complex anti aldol reaction to join the C 1–C 15 and C 16–C 28 spiroketal regions, and an anomeric sulfone acylation to join the C 29–C 37 and C 38–C 43 pyran regions. The incorporation of the C 44–C 51 sidechain in the final stages of the synthesis establishes a viable route for the construction of variants in this pharmacologically important region. Methodological developments en route to the total synthesis include a 1,5 anti-selective methyl ketone aldol reaction and a diastereoselective approach to Lewis acid mediated β- C-glycosidation. Completion of the synthesis has confirmed the stereochemical assignments proposed in the altohyrtin series and has established the identity of the altohyrtin and spongistatin marine macrolides. The first total synthesis of a spongipyran macrolide, altohyrtin C, is described. Completion of the synthesis has confirmed the stereochemical assignments proposed in the altohyrtin series and has established identity of the altohyrtin and spongistatin marine macrolides.