Cycloaddition and one-carbon homologation studies in the synthesis of advanced iridoid precursors

• Published in: Organic & biomolecular chemistry Vol. 7; no. 17; pp. 3527 - 3536
• Main Authors: Stevens, Anne T., Caira, Mino R., Bull, James R., Chibale, Kelly
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2009
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemistry; Carbon - chemistry; Chemistry; Chemistry, Organic; Crystallography, X-Ray; Glucosides - chemistry; Iridoid Glucosides; Iridoids - chemical synthesis; Iridoids - chemistry; Molecular Conformation; Organic Chemistry Phenomena; Physical Sciences; Science & Technology; ORGANIC-SYNTHESIS; KETONES; DIELS-ALDER; NITRILES; BUILDING-BLOCKS; LEVOGLUCOSENONE; RIBONOLACTONE; SYSTEMS; CHIRAL BUTENOLIDES
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b902452b

A Diels-Alder cycloaddition approach to the sweroside aglycone intermediate of iridoids was explored using silylated butenolides and levoglucosenone as dienophiles under both Lewis acid and thermal conditions. Results of this study reveal no evidence that using less sterically demanding derivatives compromise the diastereofacial selectivity of the cycloaddition using silylated butenolides. Further chemistry performed on cycloadducts concentrated on the identification and management of methodologies suitable for its conversion into sweroside aglycone. During the course of these studies, a dehydrative cyclisation onto a preformed tetrahydrofuran ring to a bis-tetrahydrofuranoid moiety was unravelled. In addition studies on levoglucosenone-derived cycloadducts provide extensive insight into the conformational behaviour and reactivity. Further, the X-ray crystal structure of an alcohol intermediate from one-carbon homologation studies provided the first structural evidence confirming the diastereoselectivity of the cycloaddition procedure.