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Various intermediates for the synthesis of erythronolide A, an aglycon of erythromycin A, are prepared from the corresponding seco-acids using 2-methyl-6-nitrobenzoic anhydride (MNBA) in the presence of 4-(dimethylamino)pyridine (DMAP) with or without triethylamine. The efficiency of the MNBA lactonization is assessed by studying this method and comparing the results with those of the other established macrocyclization protocols. It has been finally concluded that (i) the conformationally appropriate substrate for the monomeric cyclization gave the desired lactone in excellent yield under mild reaction conditions in the presence of MNBA and DMAP, (ii) the highly-strained substrate for the cyclization also afforded the monomeric lactone in relatively good yield at 100°C in toluene, and (iii) the seco-acid having stable linear conformation, which preferred dimerizing more than forming the monomeric lactone, provided the corresponding diolide in high yield with the constant ratio of the monomer to dimeric lactone (approximately 1/5). © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 305–320; 2009: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.200900017

We have developed effective methods for the total synthesis of 2-hydroxytetracosanolide and 2-hydroxy-24-oxooctacosanolide, the defensive salivary secretions of termites. The former natural product isolated from Armitermes neotenicus, a species of termite that inhabits Guyana, contains a 25-membered lactone backbone, and the latter, extracted from Pseudacanthoterme springer, an African termite, includes a 29-membered lactone moiety. The key cyclization to produce the 25- or 29-membered lactone core is performed by using 2-methyl-6-nitrobenzoic anhydride (MNBA) with a stoichiometric amount of 4-(dimethylamino)pyridine (DMAP) or a catalytic amount of 4-(dimethylamino)pyridine N-oxide (DMAPO).

A new method for the total asymmetric synthesis of antitumor agent Taxol is described. Baccatin III, a complex carbon framework, is synthesized by way of B to BC to ABC ring construction. Further, a method of forming Taxol from baccatin III and a β-amino acid is also demonstrated.

Optically active 7-t-butyldimethylsiloxy-4,8-dibenzyloxy-6,6-dimethyl-5-p-methoxybenzyloxy-2-cycloocten-1-one (1) was synthesized from 3,7-dibenzyloxy-4,8-di-t-butyldimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone (2) by way of intramolecular Reformatsky-type reaction using SmI2.

Optically active 9-t-butyldiphenylsiloxy-11,11-dimethyl-5-methoxymethoxy-1,2,6-tribenzyloxybicyclo[5.3.1]undec-3,7-diene (12) was synthesized from diketone 9 via an intramolecular aldol reaction. The diketone 9 was synthesized from 7-t-butyldimethylsiloxy-4,8-dibenzyloxy-6,6-dimethyl-5-p-methoxy-benzyloxy-2-cycloocten-1-one (1) by way of a two-step sequence using diastereoselective allylation with allylmagnesium bromide followed by Wacker oxidation.

Optically active novel taxoids were efficiently synthesized from 8-membered ring compound 3 by successive constructions of BC and ABC ring systems via each intramolecular aldol and intramolecular pinacol coupling reactions.

Optically active 2α,10β-dibenzyloxy-11β-(t-butyldimethylsiloxy)-7β-hydroxy-1α-(4-methoxybenzyloxy)–8β,15,15-trimethyl-4-methylene-trans-bicyclo[6.4.0]dodecan-9-one 2 that corresponds to BC ring system of Taxol was prepared from 8-membered ring enone 3 in high yield via stereoselctive Michael addition and successive intramolecular aldol cyclization. The above 8-membered ring enone 3 was synthesized from the linear optically active polyoxy-compound 4 by SmI2-mediated intramolecular aldol cyclization.

Baccatin III was efficiently synthesized from the BC ring system of Taxol,2α,10β-dibenzyloxy-11β-(t-butyldimethylsil-oxy)-7β-hydroxy-1α-(4-methoxybenzyloxy)-8β,15,15-trimethyl-4-methylene-trans-bic...

An efficient method for the synthesis of (−)-cephalosporolide D was established via successive enantioselective aldol reaction and effective construction of 8-membered ring lactone moiety.

Optically active novel 18-demethyltaxiods were successfully synthesized from 2α,10β-dibenzyloxy-11β-(t-butyldimethylsiloxy)-7β-hydroxy-1α-(p-methoxybenzyloxy)-8β,15,15-trimethyl-4-methylene-trans-bicyclo[6.4.0]dodecan-9-one (2) which corresponds to the BC ring system of Taxol by stereoselective allylation and intramolecular aldol condensation reactions.

A new method for the synthesis of optically active anti-vic-hydroxymethyl units that correspond to anti-aldol derivatives is developed by way of successive enantioselective aldol and diastereoselective desulfurization reactions.

A novel [1,3] sigmatropic rearrangement of ketene silyl acetals derived from benzyl α-substituted propanoates is developed. The reaction of ketene silyl acetal derived from optically active 1-phenylethyl 2-methylpropanoate mainly proceeds with the retention of chirality at the benzyl position to give the corresponding optically active silyl ester under thermodynamic conditions.

The first asymmetric total syntheses of botcinins A-F, homobotcinin E, botcinic acid, botcinic acid methyl ester, botcineric acid, and 3-O-acetylbotcinic acid methyl ester were achieved. The structures of these compounds have been unequivocally determined through their total syntheses and those of botcinin A, botcinin B, botcinin E, homobotcinin E, botcinic acid, botcinic acid methyl ester, botcineric acid, and 3-O-acetylbotcinic acid methyl ester are identified with the revised forms of the natural products formerly assumed to be 3-O-acetyl-2-epibotcinolide, 3-O-acetyl-2-epihomobotcinolide, 2-epibotcinolide, 2-epihomobotcinolide, botcinolide, 4-O-methylbotcinolide, homobotcinolide, and 3-O-acetyl-5-O-methylbotcinolide, respectively. It was further proved that the proposed nine-membered ring structure of 2-epibotcinolide is very unstable and the ineluctable translactonization easily occurred to form the corresponding γ-lactone.

The stereoselective total syntheses of botcinins A (1) and B (2), and homobotcinin E (4), a homologue of botcinin E (3), have been achieved starting from a polyoxygenated tetrahydropyran intermediate 15 via formation of botcinic acid (12) and botcineric acid (13). Through the total syntheses, three actual relationships are revealed, that is, (i) the structure of botcinin A (1) is identical with the revised structure of the natural compound, which was formerly assumed to be 3-O-acetyl-2-epibotcinolide (5), (ii) the structure of botcinin B (2) is identical with the revised structure of the natural compound, which was supposed to be 3-O-acetyl-2-epihomobotcinolide (6), and (iii) the structure of the natural compound formerly assumed to be 2-epihomobotcinolide (8) must be revised to that of homobotcinin E (4).

The first asymmetric total syntheses of botcinins C (18), D (19), E (20), and F (21), botcinic acid (22), botcinic acid methyl ester (23), botcineric acid (26), and 3-O-acetylbotcinic acid methyl ester (27) were achieved. The structures of these compounds have been unequivocally determined through their total syntheses and those of 20, 22, 23, 26, and 27 are identified with the revised forms of the natural products formerly assumed to be 2-epibotcinolide (10), botcinolide (6), 4-O-methylbotcinolide (7), homobotcinolide (11), and 3-O-acetyl-5-O-methylbotcinolide (8), respectively. It was further proved that the proposed nine-membered ring structure of 2-epibotcinolide (10) is very unstable and the ineluctable translactonization easily occurred to form the corresponding γ-lactone57.

[Structure: see text] The total synthesis of pseudo 2-epibotcinolide (1b) through several featured synthetic approaches has been attained. First, the chiral linear precursors of the nine-membered ring compound is stereoselectively constructed by the asymmetric aldol reaction for producing beta-hydroxy ester units. Second, the key cyclization reaction to form the nine-membered lactone moiety is efficiently achieved by the extremely facile and powerful mixed-anhydride method promoted by 2-methyl-6-nitrobenzoic anhydride (MNBA) with basic promoters.

Various carboxamides or peptides are synthesized from the corresponding carboxylic acids and amines or α-amino acids using 1,1′-carbonyldioxydi[2(1H)-pyridone]. The reaction proceeds in the absence of basic promoters such as triethylamine or 4-(dimethylamino)pyridine, therefore, the undesired racemization does not occur at all in the segment coupling producing Z-Gly-Phe-Val-OMe and Z-Phe-Val-Ala-OMe.

An effective method for the preparation of 8-membered ring enone, (4S,5R,7R,8R)-4,8-bis(benzyloxy)-7-(t-butyldimethylsiloxy)-5-(4-methoxybenzyloxy)-2,6,6-trimethylcyclooct-2-enone (1), in sufficien...