Carbocyclic Nucleoside Analogs. 1. Concise Enantioselective Synthesis of Functionalized Cyclopentanes and Formal Total Synthesis of Aristeromycin

Abstract

An enantioselective synthesis of functionalized cyclopentanes has been used to access carbocyclic nucleoside analogs. This pathway allows access to carbocyclic C- or carbocyclic N-nucleosides from a common intermediate, ester 16. Additionally, (1R,2R,3S,4R)-4-amino-2,3-dihydroxy-1-cyclopentanemethanol (18), an intermediate in the total synthesis of aristeromycin, has been prepared as a single enantiomer in eight isolated steps from cyclopentadiene. Progress toward the synthesis of novel carbocyclic C-nucleosides is also discussed.

Variable Strategy toward Carbasugars and Relatives. 4.1 Viable Access to (4a-Carbapentofuranosyl)amines, (5a-Carbahexopyranosyl)amines, and Amino Acids Thereof

“…As expected, treatment of 20 and 21 with NaBH 4 in wet THF cleanly led to the corresponding protected cyclopentanoids 22 and 23 (88% and 98% yields), which were finally fully liberated by acidic treatment (aq HCl, THF, MeOH) followed by DOWEX (H + form). 4a-Carba-β -d -xylofuranose ( 1 ) 2b and 4a-carba-β- d -ribofuranose ( 2 ) were isolated in 95% and 99% yields, which correspond to 34% and 10% overall yields from the starting pyrrole 9 (12 steps each).…”

Enantioselective Synthesis of a Hydroxymethyl-cis-1,3-cyclopentenediol Building Block

“…Functionalized cyclopentanol frameworks are an important structural motif in organic chemistry. Scaffolds of this type are found in many biologically active natural products, pharmaceuticals, and nucleoside analogs . In particular, cis -1,3-cyclopentanediols ( 1 ) have been extensively employed in the synthesis of medicinally relevant natural and non-natural compounds. , For example, the biologically active prostaglandin (e.g., 2 and 3 ), , furanocembranoid diterpene (e.g., 4 and 5 ), and norcembranoid diterpene families of natural products (e.g., 6 and 7 ) , all contain the cis -1,3-cyclopentanediol motif (Figure ).…”

Preparation of Carbocyclic C‐Nucleosides from α‐Chlorooxime Precursor

“…Recently, Wamhoff et al proposed a novel synthetic approach to purine-like Cnucleosides from C-glycosidic tosyloximino nitrile precursors. [20] Carbocyclic C-nucleosides have been obtained from an amide [21] or from a cyanoacetate. [22] A retrosynthetic analysis indicates that -cyclopentyl carbocyclic C-nucleosides can be prepared by direct cyclocondensation of a desired heterocyclic precursor with a functionalized C-chlorooxime.…”