1 SYNTHESIS OF CLERODIN HOMOLOGUE 2 : A SYNTHETIC APPROACH OF STRUCTURE-ACTIVITY RELATIONSHIPS
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I. 1.1-t-Butyl-7-hydroxy perhydrofuro [2,3-b] furan 1 which was selected asamodel compound about the antifeeding active center of the neo-clerodane diterpenes and that was synthesized via a furan-alcohol which was derived by a coupling reaction with an epoxide and Li di(3-furyl)cuprate. Although 1 of diastereomeric mixture could not separated on TLC etc., its lactone derivative gave lactone a and b as a fine crystal. Configurations of their H^1 protons could not determined from the nmr spectra, since their coupling constants had approximately the same values to each others. Then we decided successfully the configuration of the protons and the conformation of the compounds by the combination of the LIS experiments (LIS) and the empirical force-field calculation (EFF). I. 2. We reported that the synthesis of the clerodin homologue 3 for investigation of the structure-activity relationship. However, it was very difficult to determine the C^<11> configuration on the epoxy-acetonide 8 of the synthetic intermediate. Thus, we synthesized the diastereomeric hydroxy-acetonide A (9) and B (10) via an epoxidation reaction by mCPBA or NBS. Each C^<11> configuration of the derivatives was determined by the EFF-LIS combination method, as well as lactone a and b, as shown in Fig. 2. II. Mono and disubstituted benzene derivatives were synthesized for clarifing the stabilization of the perhydrofuro[2,3-b]furan ring by steric effect. It is noteworthy that the furo-furan derivative from sym-m-xylenol detected as a 1: 1 mixture of 4 and 11+12 on NMR, whereas ca. 90% amounts of dimethyl benzene derivative 18 existed in the perhydrofuro[2,3-b]furan ring form.
