Masayuki Kitagawa

Synthesis and antiviral activity of oxetanocin derivatives

Abstract The sugar part of natural oxetanocin A was chemically modified. Some of the derivatives demonstrated strong antiviral activity against human immunodeficiency virus (HIV).

The first total synthesis of calbistrin A, a microbial product possessing multiple bioactivities

Abstract The octahydronaphthopyranone moiety is synthesized from methyl α- d -mannopyranoside through the intramolecular Diels-Alder reaction, and the tetraenedicarboxylic acid moiety is from the enzymatically prepared anti-compound. Both moieties were coupled to accomplish the total synthesis of calbistrin A and to disclose its absolute structure.

Mechanism of inhibition of human cytomegalovirus replication by oxetanocin G

Oxetanocin G(9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine, OXT-G) is a potent and selective agent against human cytomegalovirus (HCMV). In this study we synthesized the triphosphate form of OXT-G, OXT-GTP, and examined its effect on the activities of HCMV DNA polymerase, herpes simplex type 2 (HSV-2) DNA polymerase and human DNA polymerase alpha. OXT-GTP was found to inhibit all these polymerases in a competitive manner with respect to dGTP. The Km for dGTP and the Ki for OXT-GTP of HCMV DNA polymerase were 0.86 and 0.53 mu M, respectively, while the corresponding values of DNA polymerase alpha were 2.2 and 3.6 mu M, respectively. HPLC analysis using [3H]OXT-G also revealed that OXT-G was converted to its triphosphate form 7- to 8-fold more efficiently in HCMV-infected cells than in uninfected cells. The results suggest that both the preferential phosphorylation of OXT-G in HCMV-infected cells and the preferential inhibition of HCMV DNA polymerase by OXT-GTP may contribute towards the selective activity of OXT-G against HCMV replication.

Total synthesis of an acaricide, Gualamycin

Abstract The first enantiospecific total synthesis of gualamycin has been accomplished by coupling the thioglycoside of the amino-disaccharide portion with the strained di-O-benzylidene derivative of the pyrrolidine-aglycone.

Enantioselective Synthesis of Pyrizinostatin, a Pyroglutamyl Peptidase Inhibitor

Enantiospecifically pure pyrizinostatin was synthesized from 2-methyl- fervenulone by using chiral imines of acetone

One-Step Synthesis and Enzyme Inhibiting Activities fo Pyrizinostatin Analogs

Pyrizinostatin analogs were synthesized from 2-methylfervenulone and a variety of methyl ketones in only one step and showed stronger enzyme inhibiting activities than pyrizinostatin itself

Cystacyclin, a novel microbial metabolite with NGF mimetic activity.

Nerve growth factor (NGF) is known to have key roles in neural protection and repair of central and peripheral neurons.1 NGF was reported to ameliorate several neuronal dysfunction and injury in animal models,2, 3 and has been applied to clinical trial.4 Because of its protein property, NGF is thought unsuitable for oral administration and insufficient for blood–brain barrier penetration. So far low-molecular-weight compounds having NGF mimetic activity have been screened and neurite-inducing compounds such as lactacystin5 and K-252a6 were isolated from microbial resources. A chemically synthesized compound of AIT-012 was reported to enhance NGF-induced neurite outgrowth and has been applied to clinical trail.7 In this report we describe isolation of a novel NGF mimetic compound and show its physico-chemical properties and biological activities of the compound named as cystacyclin.