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The first total synthesis of antifungal cyclic depsipeptide aureobasidin A is described. The synthesis was achieved mainly using bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) as a coupling reagent. Peptide cyclization was carried out between L- allo -isoleucine (L- a lle 1 ) and L- Pro 9 residues in the linear nonapeptide at the final step of the synthesis. Synthesized aureobasidin A was completely identical with the natural antibiotic with respect to antifungal activity and physicochemical properties. Unusual reactions due to N -methylamino acid, an oxazoline-mediated reaction and an N , O -acyl migration, are also described.

A spider toxin NSTX-3 obtained from the venom of Papua New Guinean spider, Nephila maculata was synthesized in order to confirm its proposed structure and to supply the sample for the biological tests. The structure of NSTX-3 is now established as 2,4-dihydroxyphenylacetyl-L-Asn→Cad←Pua←L-Arg, where Cad stands for cadaverine and Pua for putreanine.

In a study on structure-activity relationship of spider toxin NSTX-3 obtained from venom of Nephila maculata, nine analogs or fragments of natural toxin were synthesized. Among them, des-Arg- NSTX-3 was found to be the minimum structure for blocking the excitatory transmission in the crustacean neuromuscular synapse. A positive charge of the arginine part was concluded to play the most important role for exhibition of the activity.

Clavamine, a new insecticidal toxin isolated from the venom of Joro spider (Nephila clavata) was totally synthesized in order to confirm the proposed structure. In clavamine, a fragment of glycylalanine is inserted in the structure of NSTX-3, a New Guinean spider toxin. The synthesis determined the chemical structure of clavamine unambiguously.

The structure of lepidopteran was determined by sequential analysis using the Edman method for the whole molecule as well as several fragment peptides obtained by enzymatic and chemical cleavages. Consequently, lepidopteran was found to be a mixture of congeners composed of 35 amino acids possessing one replaceable amino acid residue of lysine with δ-hydroxylysine.

Silkworm, Bombyx mori , produces self-denfense substance lepidopteran in a haemolymph when it is vaccinated with killed Escherichia coli . Lepidopteran family contains at least three congeners A, B and C, all of which were isolated and determined in amino acid sequences. Furthermore, total synthesis of lepidopteran A was achieved. For elucidation of structure-activity relationship of lepidopteran, twenty one different kinds of peptide fragments were then synthesized. From results of antibacterial tests for those peptides, it is concluded that N-terminal region particularly the Arg -Trp2 sequence is very important for exhibition of the biological activity. The minimal sequence of lepidopteran providing significant bioactivity is the peptide fragment (1–18). α-Helix content in the peptide chain does not necessarily guarantee a manifestation of the activity. An important factor to strengthen the activity seems to be a hydrophobicity in the molecule in addition to the N-terminal region. The assumption was confirmed by preparation of long aliphatic amide of the fragment (1–18) which showed almost comparable activity to that of the original lepidopteran.

Two new ureido amino acids, lividine ( 1 ) and grateloupine ( 2 ), were isolated from Grateloupia livida and Grateloupia filicina respectively. The structures of both amino acids were assumed mainly by NMR spectra and determined as N w -carbamoyl-L-citrulline for lividine and as N -carbamoyl- Y -aminobutyric acid for grateloupine by comparison with the synthetic compounds respectively.

Total syntheses have been achieved of capreomycin IA and IB according to our newly proposed structures. The β-lysine residue in the branch was introduced to the cyclic peptide moiety which was prepared by cyclization of the corresponding pentapeptide. Deprotection followed by conversion of β,β-diethoxyalanine residue to β-ureidodehydroalanine residue afforded the desired products, which were identical with natural capreomycins in all respects.

The structure of putreanine, a new amino acid isolated from mammalian brain, was studied by its dissociation constants, mass spectrum, NMR spectrum and ORD. The structure N-(4-aminobutyl)-3-aminopropionic acid was assigned to it from the results obtained. This amino acid was synthesized by condensation of 4-phthalimino-1-bromobutane and ethyl β-alaninate followed by add hydrolysis. The identity of the synthetic compound with the natural amino acid confirmed the structural assignment.