| Following the intramolecular Diels-Alder (IMDA) strategy, an assumption for the further study on the total synthesis of Hainanolide was proposed. It was suggested that the lactone ring (ring E) should be accessed before the construction of ring F and A. According to such assumption, the previously studied IMDA reaction was duplicated, and the ratio of cyclo-additive 10 and 11 was re-determined. Starting from the two compounds, three aspects of work, aiming at the construction of 1,4-lactone, were designed and carried out:1. Revising the C2a stereochemistry with the existing C3-β,C4-α-dihydroxy:a) Starting from compound 10 (C2a-α-H), the C1 decarboxylated derivative 33 was synthesized. After an investigation on the epoxidation of 33 and subsequent oxane ring opening, the C3-β, C4-α -dihydroxyl group was successfully introduced, in accordance with the diaxial rule.b) In order to convert the C2a-α-H into C2a- β-H, a C3-oxo-group was introduced after the C4-β-hydroxyl group was selectively protected with MOM. But further epimerization of 41 took place at C4, while the C2a-H remained to take the α orientation. The possible reasons were proposed.c) Starting from the C3-β,C4-β -dihydroxy group protected compound 43, a C2-oxo-group was introduced. Yet subsequent attempts to epimerize the C2a-α-H was obliged to be given up, because the intermediate 46 is unstable on exposure to base.2. Introducing the C3-β ,C4-α-dihydroxy after revising the C2a stereochemistry:a) The C2a-β-H tricyclic-4-one 18, as well as intermediate 15 and 17, was obtained through the previously established process.b) In order to get the Δ(3,4) C2a-β-H tricyclic olefin 31, the reduction of 17's tosylhydrozone derivative with catechol-borane and that of 15 with NaBH4-NiCl2 was investigated. The expected compound 31 was obtained in the form of mixture.c) The mixed reduction products of 15 were directly exposed to epoxidation and oxane ring opening, and the structure of 31 was thus confirmed. Yet, completely differ from the cases of C2a- α -H, the C3-α ,C4-β-dihydroxyl group was introduced after subsequent epoxidation and oxane ring opening of the Δ3,4 C2a-β-H tricyclic olefin.d) By oxidation of the kinetic enol ether of 18, the desired C3-β-hydroxy group was introduced. Thus, the problem of relative stereochemistry concerning the lactone ring E was solved. Lactonization of 32 swiftly took place under basic condition, and the first four-ring intermediate 53 was gained.3.The singlet oxygen oxidation of tricyclic olefins and the improved route to... |
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