Synthesis of the spirosuccinimide moiety of Asperparaline A.

2,6,6-Trimethyl-2-azaspiro[4.4]nonane-1,3-dione (9), a spirosuccinimide moiety of asperparaline A (1), was synthesized by starting from 2,2-dimethylcyclopentanone (4) via trinitrile 6 in five steps in a moderate yield. This conversion establishes a model study for synthesis of the spirosuccinimide moiety of asperparaline A (1).

Kinetic analysis of the reaction catalyzed by chitinase A1 from Bacillus circulans WL-12 toward the novel substrates, partially N-deacetylated 4-methylumbelliferyl chitobiosides.

The kinetic behavior of chitinase A1 from Bacillus circulans WL-12 was investigated using the novel fluorogenic substrates, N-deacetylated 4-methylumbelliferyl chitobiosides [GlcN-GlcNAc-UMB (2), GlcNAc-GlcN-UMB (3), and (GlcN)(2)-UMB (4)], and the results were compared with those obtained using 4-methylumbelliferyl N, N'-diacetylchitobiose [(GlcNAc)(2)-UMB (1)] as the substrate. The chitinase did not release the UMB moiety from compound 4, but successfully released UMB from the other substrates. k(cat)/K(m) values determined from the releasing rate of the UMB moiety were: 145.3 for 1, 8.3 for 2, and 0.1 s(-1) M(-1) for 3. The lack of an N-acetyl group at subsite (-1) reduced the activity to a level 0.1% of that obtained with compound 1, while the absence of the N-acetyl group at subsite (-2) reduced the relative activity to 5.7%. These observations strongly support the theory that chitinase A1 catalysis occurs via a 'substrate-assisted' mechanism. Using these novel fluorogenic substrates, we were able to quantitatively evaluate the recognition specificity of subsite (-2) toward the N-acetyl group of the substrate sugar residue. The (-2) subsite of chitinase A1 was found to specifically recognize an N-acetylated sugar residue, but this specificity was not as strict as that found in subsite (-1).

Chemo- and enzymatic synthesis of partially and fully N-deacetylated 4-methylumbelliferyl chitobiosides: fluorogenic substrates for chitinase.

Partially and fully N-deacetylated 4-methylumberlliferyl chitobioside (1) derivatives, such as GlcN-GlcNAc-UMB (2), GlcNAc-GlcN-UMB (3), and (GlcN)2-UMB (4), were synthesized using chemo- and enzymatic procedure. Fluorescent aglycon was released from the chitobiosides 1, 2 and 3 by the action of chitinase. These UMB glycosides of heterochitobiose were versatile probes for the investigation of substrate binding chitinase from various sources.

Simple Synthesis of Both Enantiomers of the C7-C12 Segment of Epothilones.

Both enantiomers of the C7-C12 segment (3 and 4) of antitumor antibiotics epothilones (1and 2) were synthesized from methyl (R)- and (S)-3-hydroxy-2-methylpropionate (5 and 6) in five steps in a fair yield.

A new nucleophilic ring opening of an activated cyclopropane and a formal synthesis of (+/-)-carbovir.

The reaction of bicyclo[3.1.0]hexane 1, possessing a doubly activated cyclopropane ring, with acetic acid and potassium acetate in DMSO proceeded smoothly to give the adduct 2 in good yield. A formal total synthesis of the potent anti-HIV agent (+/-)-carbovir (9) was done by converting 2 into a known precursor 8 in 8 steps via allyl alcohol 7 including the regioselective introduction of a double bond (4 to 5) and attachment of the nucleobase using the Mitsunobu reaction (7 to 8).

Nisamycin, a new manumycin group antibiotic from Streptomyces sp. K106. II. Structure determination and structure-activity relationships.

Nisamycin, a novel manumycin group antibiotic, was isolated from the culture broth of Streptomyces sp. K106. Structural elucidation of nisamycin was achieved by detailed NMR spectral analyses and comparison of the NMR data of nisamycin with those of other manumycin group antibiotics. The structure was confirmed by chromic acid oxidation. The absolute stereochemistry of nisamycin was determined to be 4R, 5S and 6R from the CD spectra of nisamycin and chromic oxidation of nisamycin. In addition, some structure activity-relationships were examined.