Synthesis of Bradyrhizose from d-Glucose

Abstract

We describe the synthesis of the unusual bicyclic sugar bradyrhizose in 14 steps and 6% overall yield from D-glucose. The synthesis involves the elaboration of a trans-fused carbocyclic ring onto the pre-existing glucopyranose framework followed by adjustment of the oxidation levels. Key steps include radical extension of the glucopyranose side chain, ring closing metathesis, allylic oxidation, Luche reduction, hydroxy-directed epoxidation and acid-catalyzed epoxide opening at the more substituted position.

Synthesis and Antibacterial Activity of Propylamycin Derivatives Functionalized at the 5′′- and Other Positions with a View to Overcoming Resistance Due to Aminoglycoside Modifying Enzymes

“…A variety of transitionmetal-based photocatalytic systems have been employed to promote the coupling of alkyl iodides with allyl phenyl sulfone and its congeners, including palladium-and manganese-based catalysts 22,23 and iridium-based systems 24 typically in the presence of a tertiary amine as a sacrificial electron source, and indeed we have employed one such Ir-based system in our laboratories in the course of a synthesis of bradyrhizose. 25 Here, we elected to examine the metal-free 1,3,4,5-tetra(Ncarbazolyl)-2,6-dicyanobenzene (4-CzIPN) photocatalyst in combination with triethylamine as an overall reductant 26,27 as applied recently to allylation of alkyl iodides with allyl phenyl sulfone as a trap. 28 Working with N-tert-butyloxycarbonyl-4iodopiperidine, we were able to reproduce the literature photocatalytic allylation reaction 28 but were frustrated to find that application of the same conditions to iodide 25 resulted none of the elimination product 27, thereby clearly demonstrating the configuration sensitive nature of the elimination reaction.…”

“…In addition to the allylation of 25 by the action of allyl phenyl sulfone with initiation by triethylborane and oxygen, which mirrored the earlier synthesis of propylamycin itself (Scheme ), we chose to briefly explore the use of photocatalytic initiation for allylation. A variety of transition-metal-based photocatalytic systems have been employed to promote the coupling of alkyl iodides with allyl phenyl sulfone and its congeners, including palladium- and manganese-based catalysts , and iridium-based systems typically in the presence of a tertiary amine as a sacrificial electron source, and indeed we have employed one such Ir-based system in our laboratories in the course of a synthesis of bradyrhizose . Here, we elected to examine the metal-free 1,3,4,5-tetra­( N -carbazolyl)-2,6-dicyanobenzene (4-CzIPN) photocatalyst in combination with triethylamine as an overall reductant , as applied recently to allylation of alkyl iodides with allyl phenyl sulfone as a trap .…”

Metathesis Reactions in Natural Product Fragments and Total Syntheses

“…Finally, RCM of 394 in the presence of unconventional Grubbs’ precatalyst 10 followed by desilylation of t ‐butyldimethylsilyl ether with HF ⋅ py and cleavage of acetonide groups with aqueous HCl completed the total synthesis of the (11 R ,13 S ,14 R ,15 R )‐ lytophilippine A diastereomer. Captivatingly, Crich and co‐workers accomplished the synthesis of bradyrhizose 399 utilizing RCM (Scheme 54), a unique bicyclic sugar responsible for nitrogen fixation in tropical leguminous Aeschynomenes [235] . Addition of vinylmagnesium bromide to ketone 396 afforded an allylic alcohol 397 , which was then submitted to RCM in the presence of G‐II catalyst to furnish the bicyclic compound 398 .…”

“…Captivatingly, Crich and co-workers accomplished the synthesis of bradyrhizose 399 utilizing RCM (Scheme 54), a unique bicyclic sugar responsible for nitrogen fixation in tropical leguminous Aeschynomenes. [235] Addition of vinylmagnesium bromide to ketone 396 afforded an allylic alcohol 397, which was then submitted to RCM in the presence of G-II catalyst to furnish the bicyclic compound 398. After several steps, 398 was transformed into the required bradyrhizose.…”

Exploring a De Novo Route to Bradyrhizose: Synthesis and Isomeric Equilibrium of Bradyrhizose Diastereomers≠

“…These compounds were then converted into a panel of disaccharides containing both d ‐ and l ‐forms of the monosaccharide [7] . Shorter routes to the monosaccharide were then reported by Ngoje and Crich (14 steps and 6 % yield from d ‐glucose), [8] and by Matsushima and coworkers (for the bradyrhizose methyl glycoside, in 15 steps and 16 % yield) [9] . Branched octoses that are structurally analogous to d ‐bradyrhizose have also been prepared [10] …”