Total syntheses of natural tubelactomicins B, D, and E: establishment of their stereochemistries

Total syntheses of the antimicrobial tricyclic 16-membered macrolides, (+)-tubelactomicin B, (+)-tubelactomicin D, and (+)-tubelactomicin E, have been accomplished for the first time with common synthetic approaches. These total syntheses established the relative and absolute configurations of the three tubelactomicins, for which planar structures had solely been reported. The total synthesis of (+)-tubelactomicin D included a newly developed stereoselective intramolecular Diels-Alder reaction for constructing the highly functionalized octahydronaphthalene substructures.     

Highly Enantio- and s-trans C=C bond selective catalytic hydrogenation of cyclic enones: alternative synthesis of (-)-menthol

A highly enantioselective catalytic hydrogenation of cyclic enones was achieved by using the combination of a cationic Rh(I) complex, (S)-5,5'-bis{di(3,5-di-tert-butyl-4-methoxyphenylphosphino)}-4,4'-bi-1,3-benzodioxole (DTBM-SEGPHOS), and (CH2CH2PPh3Br)2. The presence of an s-cis C=C bond isopropylidene moiety on the cyclic enone influenced the enantioselectivity of the hydrogenation. Thus, the hydrogenation of 3-alkyl-6-isopropylidene-2-cyclohexen-1-one, which contains both s-cis and s-trans enones, proceeded in excellent enantioselectivity (up to 98 % ee). To obtain high enantio- and s-trans selectivities, the addition of a halogen source to the cationic Rh complex was the essential step. With the key step of the s-trans selective asymmetric hydrogenation of piperitenone, we demonstrated a new synthetic method for optically pure (-)-menthol via three atom-economical hydrogenations. Moreover, we found that the complete s-trans and s-cis C=C bond selective reactions were also realized by the proper choice of both the chiral ligands and halides.