Nucleosides. LXV. Synthesis of New Pteridine–N8–Nucleosides
A general synthetic approach to various isoxanthopterin‐nucleosides starting from 6‐methyl‐2‐methylthio‐4(3H), 7(8H)‐pterdinedione (1) has been developed. Ribosylation with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐d‐ribofuranose via the silyl‐method led to 2 and reaction with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐d‐ribofuranose using the DBU‐method afforded 28. Protection of the amide function at O4 by benzylation to 5 and by a Mitsunobu reaction with 2‐(4‐nitrophenyl)ethanol to 29 gave soluble intermediates which can be oxidized to the corresponding 2‐methylsulfonyl derivatives 8 and 30, respectively. Nucleophilic displacement reactions of the highly reactive 2‐methylsulfonyl functions by various amines proceeded under mild conditions to isoxanthopterin‐N8‐ribo‐ (11–17) and 2′‐deoxyribomucleosides (31–33). Debenzylation can be achieve by Pd‐catalyzed hydrogenation (9 to 19) and cleavage of the npe‐protecting group (31, 32 to 34, 35) works well with DBU by β‐elimination. #See Ref. 1. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.
Bicyclic 6-6 Systems: Pteridines
This chapter outlines research on pteridines in all its published aspects covering the literature from 1996 to mid-2006. Following previous editions of this work, the review outlines the historical background to pteridine research and basic structural aspects. Physical properties, notably redox properties, and the growing number of crystal structures of pteridine metal complexes are covered. The reactivity of pteridines described principally relates to substitution at nitrogen (especially forming glycosides), nucleophilic displacements of leaving groups at carbon, organometallic coupling of halides and triflates, and side-chain oxidation and condensation. Recent developments of pteridine synthesis highlight refinements of well-established methods based either upon pyrimidines or pyrazines as precursors such that selectivity and scope can be improved. Compounds and features of special interest that have developed in the decade covered include metal complexes, nucleic acid analogues, biosynthetic pathways and mechanisms, new natural products (glycosides and alkaloids), and, in particular, medicinal chemistry (both anti-infective and anticancer compounds).
Nuclear sphingolipid metabolism.
Nuclear lipid metabolism is implicated in various processes, including transcription, splicing, and DNA repair. Sphingolipids play roles in numerous cellular functions, and an emerging body of literature has identified roles for these lipid mediators in distinct nuclear processes. Different sphingolipid species are localized in various subnuclear domains, including chromatin, the nuclear matrix, and the nuclear envelope, where sphingolipids exert specific regulatory and structural functions. Sphingomyelin, the most abundant nuclear sphingolipid, plays both structural and regulatory roles in chromatin assembly and dynamics in addition to being an integral component of the nuclear matrix. Sphingosine-1-phosphate modulates histone acetylation, sphingosine is a ligand for steroidogenic factor 1, and nuclear accumulation of ceramide has been implicated in apoptosis. Finally, nuclear membrane-associated ganglioside GM1 plays a pivotal role in Ca(2+) homeostasis. This review highlights research on the factors that control nuclear sphingolipid metabolism and summarizes the roles of these lipids in various nuclear processes.