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For the total synthesis of novel cyclodepsipeptide homophymine A, (2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid was successfully synthesized by Evans' asymmetric alkylation and the anti-selective asymmetric hydrogenation of a chiral α-amino-β-keto ester as the key steps.

Cyclic peptides from marine organisms constitute a growing class of naturally occurring cytotoxic substances. A general synthetic method for thiazole amino acids, common components of these cyclic peptides 1-7, has been developed and total syntheses of 1-7 have been achieved. In the process, dolastatin 3 with the proposed structure has been disclosed to differ from the natural material and the real structure 2 has been confirmed by its total synthesis. Patellamides with the proposed structures has been revised to be 6 by their total syntheses. Absolute configuration of ascidiacyclamide has been determined to be 4 and the structure of ulithiacyclamide has been confirmed. Ulicyclamide has been efficiently prepared in combination with solid and liquid phase syntheses. Didemnins A and B, cyclic depsipeptides with potent antitumor activity, have been prepared by condensation of the key eastern and western fragments.

An efficient synthesis of physiologically interesting diarylheptanoids has been carried out through direct C-acylation using diethyl phosphorocyanidate (DEPC) followed by Grignard reactions with aldehydes.

The extent of racemization and the coupling efficiency during the coupling of benzyloxycarbonyl-L-phenylalanyl-L-valine with L-proline tert-butyl ester were conveniently and rapidly determined by the use of high performance liquid chromatography with high accuracy. An extensive examination of various known coupling methods revealed that the coupling methods using diphenyl phosphorazidate (DPPA) and, especially, diethyl phosphorocyanidate (DEPC) afforded the best results. Reported results using DPPA and DEPC as peptide coupling reagents are also summarized (Table I).

Reaction of diphenylphosphinic azide (8) with the pyrrolidine enamine 13 of 4-isobutylpropiophenone afforded two amidines 15a and 16a, which were derived from the 1, 3-dipolarcycloadduct 14a by the expulsion of nitrogen followed by 1, 2-aryl migration (path a) and by 1, 3-dipolar elimination (path b), respectively. Although diphenylthiophosphinic azide (9) and ethyl phenylthiophosphonoazidate (10) also gave similar results, diphenyl phosphorazidate (DPPA, (C6H5O)2P(O)N3) furnished the amidine 15d formed via path a as the sole isolable product. Hydrolysis of 15d with potassium hydroxide afforded ibuprofen (3) in good yield. Other nonsteroidal antiinflammatory agents, naproxen (4), ketoprofen (5), and flurbiprofen (6), were analogously and conveniently prepared from the ketones 17, 22, and 25, respectively, by a similar three-step operation using pyrrolidine, DPPA, and potassium hydroxide. 2-(2-Dibenzofuranyl)-propionic acid (7) was also prepared from the ketone 28 by the three-step procedure.

The pyrrolidine enamine 1 of deoxybenzoin reacted with diphenyl phosphorazidate (DPPA, (C6H5O)2P (O) N3) to give two amidines, the 1, 2-migration product 7a and the 1, 3-dipolar elimination product 8a in a ratio of 77 : 23. The reaction of DPPA with the enamine 2 of benzyl 2-pyridyl ketone proceeded slightly better in the presence of boron trifluoride etherate, giving both the 1, 2-migration and 1, 3-dipolar elimination products 7b and 8b. However, the main products in the reaction of DPPA with the pyrrolidine enamine 3 of 2-phenacylpyridine were 4-phenyl-5-(2-pyridyl)-1, 2, 3-triazole (11) and diphenyl N-pyrrolidinophosphoramidate (12e). Some other 1, 3-dipolar cycloadditions of enamines with organic azides were also investigated.

DL-[n]-Gingerols (1) and their relatives, which have various interesting physiological actions, have been conveniently and efficiently prepared from ferulic acid (2) through direct C-acylation using diethyl phosphorocyanidate (DEPC) in the presence of triethylamine.

A novel one-pot and high-yield cyanophosphorylation of carbonyl compounds is achieved by treatment of ketones or aldehydes with diethyl phosphorocyani-date (DEPC) in the presence of a catalytic amount of lithium diisopropylamide in tetrahydrofuran.

Aromatic α-nitroketones can be conveniently prepared from aromatic carboxylic acids and nitromethane by the action of diethyl phosphorocyanidate (DEPC) in the presence of triethylamine.

Condensation of carboxylic acids with tert-butyl hydroperoxide has been smoothly achieved by the use of diethyl phosphorocyanidate and triethylamine under mild reaction conditions, giving tert-butyl peroxycarboxylates in good yields.

Avellanins A and B (1 and 2), new pressor-active fungal metabolites from Hamigera avellanea, have been conveniently synthesized from methyl anthranilate. This synthetic study has established the absolute stereostructure of avellanin B (2). Coupling of methyl anthranilate with N-protected amino acid derivatives was best carried out by use of ((9-fluorenylmethyl)oxy)carbonyl (Fmoc)-amino acid chloride. Chain elongation for avellanins was accomplished with diethyl phosphorocyanidate, while cyclization was achieved with diphenyl phosphorazidate.

A mixture of diethyl phosphorocyanidate (DEPC) and hydrogen peroxide in the presence of 2-hydroxypyridine or 1, 2, 4-triazole functions as an epoxidizing agent for olefins.

The synthesis of the N-terminal hexapeptide of the vasoactive intestinal peptide (VIP), His-Ser-Asp-Ala-Val-Phe (II) was carried out by the both fragment condensation and stepwise elongation approaches using mainly diphenyl phosphorazidate (DPPA) as a coupling reagent.

A derivative of D-ristosamine, the enantiomer of a carbohydrate component of the antibiotics ristomycin, has been prepared from ethyl L-lactate in a stereoselective manner using the Mitsunobu reaction as a key step.