A Concise, Efficient and Production-Scale Synthesis of a Protected l-Lyxonolactone Derivative:  An Important Aldonolactone Core

Abstract

A multikilogram-scale synthesis of l-lyxonolactone-2,3-O-isopropylidene is reported. It proceeds efficiently from an optimized, large-scale, aqueous bromine oxidation of d-ribose to d-ribonolactone including a one-pot isopropylidene formation, and subsequent conversion of the d-ribonolactone-2,3-O-isopropylidene to l-lyxonolactone-2,3-O-isopropylidene via the derived C5-mesylate and intramolecular relactonization of the product of aqueous potassium hydroxide cleavage of the d-ribonolactone ring. The inversion of configuration at the C4-chiral center is understood in terms of an intermediating C4−C5-epoxide. The overall process is noteworthy for its operational simplicity, stereochemical integrity, and use of inexpensive chemicals.

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

“…17 Protection as the 2,3-O-isopropylidene acetal (7) and activation of (9), which immediately recyclized when acidified to produce a c-lactone (10) with inversion at the 4-position. 19 This route to compound 10 from D Dribose was recently optimized 17 for use on a large scale and gives the L L-lyxonolactone derivative 10 as an easilypurified, crystalline compound in good yield.…”

The first asymmetric synthesis of marliolide from readily accessible carbohydrate as chiral template

“…18 But, our initial attempts to convert the primary alcohol into a removable group as a halide or a sulfonate proved to be failure because of unexpected decomposition of the starting material under the general halogenation 19 Ester enolate aldol reaction of dianion derived from β-hydroxy ester without protection of alcohol is well known process. 17,25 Therefore, coupling of dianion derived from β-hydroxy lactone 2 by treatment of excess LDA was conducted with myristyl aldehyde to produce an inseparable diasteromeric mixture 7 in 4:1 ratio (Scheme 2).…”

“…L-Lyxonolactone is readily accessible from D-ribose via Dribonolactone by a known simple process reported previously. 18 …”

Synthesis of Differently Protected 1‐C‐Methyl‐Ribofuranoses Intermediates for the Preparation of Biologically Active 1′‐C‐Methyl‐Ribonucleosides

“…For this reason, D-ribose has been chosen as the alternative starting material as already proposed for the preparation of kilogram scale of a few D-ribonolactone derivatives. [13,14] We have tried classical oxidations including the reactions with permanganate [13] or pyridinium chlorochromate [15] and the reagent of choice was tetrapropylammonium perrhuthenate (TPAP) under catalytic conditions with N-methylmorpholine N-oxide (NMMO) as co-oxidant. [16] This oxidizing system, previously applied to the synthesis of lactones from pyranoses and furanoses protected as benzyl and allyl ethers, [17] allowed a nearly quantitative transformation (95% of recovered purified product) of protected D-ribofuranoses 2, 3b, and 4 to the corresponding lactones 5, 6, and 7 (Sch.…”