Isolation and structural study on new O'-Glucosyl inosine form ligia exotica

Abstract

A novel purine disaccharide nucleoside was isolated from the crustacean Ligia exotica and purified by HPLC on GS 320 and ODS column. By the spectral analyses of $^1H NMR$, $^{13}C NMR$, HMQC, HMBC, NOESY, HRFAB-MS and UV spectra, the new nucleoside was expected to be 3``-O-(α-D-glucosyl) inosine. The structure of natural product was unambiguously confirmed by total synthesis. Activation of the benzyl-protected gluco-pyranosyl donor 18 with $BF_3-Et_2O$ at -10℃ in the presence of acceptor 16a led to the consumption of both starting materials and formation of a glycosylated products 19 as an approximate 8:1 mixture of α and β anomers. Silica gel column separation of the anomers is readily effected after desilylation to give the α -disaccharide 20 and its β-anomer 21. The 20 was treated with $Pd(OH)_2/C$ in the presence of cyclohexene and EtOH to give compound 13 of which spectral data were all identical with those of the natural product. Thus the structure of natural product was concluded to be 3``-O-(α -D-glucosyl)inosine. The synthesis of 13 by glucosylation of a suitably protected inosine derivative under mild conditions and its various analogues have been synthesized to test biological activities. One of the synthetic derivatives exhibited cytotoxicity against human cancer cell with $GI_50$ value of 2.31㎍/ml in vitro. In order to synthesize new quinoxaline antibiotics, cyclic octadepsipeptide 78 has been prepared from Cbz-D-Ser[BOC-Ala-MeCys(Bam)-Me-Val]-OH 72 and Cbz-D-Ser[H-Ala-MeCys(Bam)-Me-Val]-OPa 73 as a key intermediate. The protected tetradepsipeptide 71 was treated with Zn in aqueous 90% acetic acid effected reductive cleavage of the phenylacyl (Pa) ester function to provide tetradepsipeptide 72 having a free C-terminal carboxyl group. Tetradepsipeptide 73 required for fragment coupling with 72 was prepared by treatment of 71 with $TFA-CH_2Cl_2$. The coupling of 72 and 73 with DCC-HOBt in THF afforded the linear octadepsipeptide 74 in 65% yield. Th...