Total Synthesis of Lajollamycin B.

The first total synthesis of lajollamycin B, a structurally novel nitro-tetraene spiro-β-lactone/γ-lactone antibiotic, is described. The convergent synthesis involves the construction of the C8'-C11' nitrodienylstannane and its coupling with the segment prepared from the C1'-C7' ω-iodoheptadienoic acid and the right-hand heterocyclic fragment, which has been utilized for our previous syntheses of oxazolomycin A. The revision of the geometry of the terminal Δ -double bond from E to Z is also described for the structure of natural lajollamycin B.

A new method for the protection of carboxylic acids with a triisopropylsiloxymethyl group.

An effective method for the protection of carboxylic acids with a triisopropylsiloxymethyl (TIPSOCH(2)) group is described. The reactions of various carboxylic acids with C(12)H(25)SCH(2)OTIPS in the presence of CuBr(2), Et(3)N, and molecular sieves 4A afford the corresponding triisopropylsiloxymethyl esters in good yields.

Organocatalytic asymmetric syntheses of inthomycins A, B and C.

The total syntheses of (+)-inthomycin A, (+)-inthomycin B and (-)-inthomycin C, the oxazole-triene antibiotics isolated from Streptomyces sp., have been accomplished via the highly enantio- and stereoselective construction of the C1-C7 (iododienyl)aldol units by taking advantage of a Cinchona alkaloid-catalyzed asymmetric β-lactone synthesis and their isomerisation-free Stille coupling with (E)-5-(3-(tributylstannyl)allyl)oxazole.

Total synthesis of oxazolomycin A.

The first total synthesis of oxazolomycin A, a structurally novel oxazole polyene γ-lactam/β-lactone antibiotic, is described. Key features include the stereocontrolled construction of the right-hand heterocyclic core by taking advantage of an In(III)-catalyzed Conia-ene type cyclization and the asymmetric synthesis of the left-hand segment starting with a Cinchona alkaloid-catalyzed cyclocondensation of an aldehyde with an acid chloride.

Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71].

Eldecalcitol [1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3, developing code: ED-71] is an analog of active vitamin D3, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] that possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)2D3. Eldecalcitol has potent biological effects on bone and is now in preparation for approval as a promising medicine for the treatment of osteoporosis in Japan. To explore chemical structure-biological activity relationships between eldecalcitol and related analogs, we have already synthesized 1-epi-eldecalcitol, 3-epi-eldecalcitol, and 1,3-diepi-eldecalcitol with inherent biological interests of each targeted analog and evaluated their biological responses.