Kiyoshi Horita

On the selectivity of deprotection of benzyl, mpm (4-methoxybenzyl) and dmpm (3,4-dimethoxybenzyl) protecting groups for hydroxy functions

Abstract The 4-methoxybenzyl (MPM) protecting group for hydroxy functions is readily removed with DDQ in dichloromethane containing a small amount of water at room temperature. Under these neutral conditions, several other protecting and functional groups remained unchanged. 3,4-Dimethoxybenzyl (DMPM) groups are more reactive than MPM groups with DDQ. The benzyl (Bn) protecting group was removed by catalytic hydrogenation over Raney nickel. Selective deprotection of DMPM, MPM and Bn groups is also presented.

MPM (4-methoxybenzyl) protection of hydroxy functions under mild acidic conditions

Abstract In order to establish a mild protection method for hydroxy functions with a MPM (4-methoxybenzyl) group, various types of hydroxy compounds were treated with MPM trichloroacetimidate in the presence of an acid catalyst. A catalytic amount (0.3 mol %) of trifluoromethanesulfonic acid was most effective and the reaction was completed within 40 min at room temperature even for highly sterically hindered hydroxy groups.

Synthesis of erythronolide a via a very efficient macrolactonization under usual acylation conditions with the Yamaguchi reagent

Abstract Macrolactonization of 3,5- O -(3,4-dimethoxybenzylidene)-9,11- O -(2,4,6-trimethylbenzylidene)(9 S )-9-dihydroerythronolide A seco-acid ( 4 ) was reexamined under various conditions and found to proceed rapidly only by treatment of 4 with Yamaguchis reagent, 2,4,6-trichlorobenzoyl chloride, in the presence of a large excess of TEA and a small amount of DMAP at room temperature to give the corresponding 14-membered erythronolide A derivative ( 7 ) in almost quantitative yield.

Selective hydrogenolysis of the benzyl protecting group for hydroxy function with Raney nickel in the presence of the MPM (4-methoxybenzyl) and DMPM (3,4-dimethoxybenzyl) protecting groups

Abstract The benzyl protecting group for hydroxy function was selectively removed by catalytic hydrogenolysis with Raney nickel in the presence of the MPM (4-methoxybenzyl) and DMPM (3,4-dimethoxybenzyl) protecting groups, and applied to the synthesis of some synthons to macrolide and polyether antibiotics.

DMPM (3,4-dimethoxybenzyl) protecting group for hydroxy function more readily removable than MPM (p-methoxybenzyl) protecting group by DDQ oxidation

Abstract The DMPM (3,4-dimethoxybenzyl) protection for hydroxy function was deprotected more readily than the MPM (p-methoxybenzyl) protection by DDQ oxidation under neutral conditions, and applied to the synthesis of some synthons to macrolide and polyether antibiotics.

Stereoselective synthesis of erythronolide a by extremely efficient lactonization based on conformational adjustment and high activation of seco-acid1

Abstract C1-C5 sulfone (11) and C7-C15 aldehyde (20), synthesized stereoselectively from D- glucose, were coupled, and the C5 and C6 chiral centers were constructed taking advantage of the MPM (4-methoxybenzyl) type protecting group to give the seco-acid (7), which has 9,11-and 3,5- diols protected as the mesityl- and DMP (3,4-dimethoxyphenyl) acetals, respectively. When Yamaguchis mixed anhydride of 7 was treated with a high concentration of DMAP at room temperature, a very rapid cyclization occurred and the 14-membered lactone (8) was isolated in almost quantitative yield. Deprotection of 8 readily gave 9-dihydroerythronolide A (2), which was converted to the title compound (1).

Synthetic studies of 18-membered anti-tumor macrolide, tedanolide. Computer-aided conformational design of a seco-acid derivative for efficient macrolactonization

Abstract Computer-aided conformational analyses are successfully applied to the synthesis of a key intermediary 18-membered lactone of tedanolide ( 1 ). The design of a seco-acid derivative based on computation in order to achieve its efficient macro-lactonization is described.

Stereoselective synthesis of the middle (C10–C17) and right (C18–C30) segments and their coupling to complete a formal synthesis of the polyether antibiotic salinomycin☆

Abstract The middle (C10–C17) and right (C18–C30) segments of the polyether antibiotic salinomycin were stereoselectively synthesized from D-glucose, D-mannitol and ethyl L-lactate. Coupling of the two segments followed by construction of the bisketal ring system gave the C10–C30 segment, which was already converted to salinomycin by Kishi.

Completely stereocontrolled synthesis of the right fragment of salinomycin, a polyether antibiotic, by means of the chelation-controlled Grignard reaction

Abstract In the course of our synthetic study of salinomycin ( 1 ), an ionophorous polyether antibiotic, the γ-lactone ( 2 ) corresponding to the C-21∼C-30 fragment (the right fragment) of 1 was synthesized from D-mannitol and ethyl L-lactate as chiral starting materials. The complete stereocontrol for the construction of new chiral centers has been achieved by means of the chelation-controlled Grignard reaction and the tetrahydropyran synthesis via the acid catalyzed epoxide ring opening.

Synthesis of substituted tetrahydrofurans and tetrahydropyrans. 2. Stereocontrolled acid-catalyzed cyclizations

Abstract A new acid-catalyzed synthesis of thermodynamically stable 2,5-substituted tetrahydrofurans and 2,6-substituted tetrahydropyrans was developed in order to apply to the synthesis of complex polyether antibiotics.