Functionalised tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass

Abstract

Carbohydrate biomass represents a potentially valuable sustainable source of raw materials for chemical synthesis, but for many applications, selective deoxygenation/dehydration of the sugars present is necessary to access compounds with useful chemical and physical properties. Selective dehydration of pentose sugars to give tetrahydrofurans can be achieved by treatment of the corresponding N,N-dimethylhydrazones under acidic or basic conditions, with the two approaches showing complementary stereoselectivity. The dehydration process is readily scalable and the THF hydrazones derived from arabinose, ribose, xylose and rhamnose were converted into a range of useful fragments containing primary alcohol, ketone, carboxylic acid or amine functional groups. These compounds have potentially useful physiochemical properties making them suitable for incorporation into fragment/lead generation libraries for medicinal chemistry. It was also shown that L-arabinose hydrazone could be obtained selectively from a crude sample of hydrolysed sugar beet pulp. † Electronic supplementary information (ESI) available: Procedures for the preparation of all compounds, together with characterisation data and X-ray crystallographic data. CCDC 1877937 and 1877938. For ESI and crystallographic data in CIF or other electronic format see Scheme 4 Proposed mechanism for the basic cyclisation of L-arabinose hydrazone 1a and D-ribose hydrazone 1b.Scheme 5 Base mediated (a) cyclic carbonate 6a formation, (b) cyclisation of 7a. Green Chemistry PaperThis journal is Scheme 10 Synthesis of carboxylic acid 10a from (a) triol 9a and (b) hydrate 12a.∥ Tables of selected crystallographic data for 9b and 13-Br can be found in the ESI. † CCDC 1877937 and 1877938 contain the supplementary crystallographic data for compounds 9b and 13-Br respectively. ¶ The selectivity of the acetal protection was confirmed by obtaining an X-ray crystal structure of 13-Br,∥ an analogue of 13 prepared from 4-bromobenzaldehyde (see ESI † for full details). Green Chemistry PaperThis journal is

Switching between X-Pyrano-, X-Furano-, and Anhydro-X-pyranoside Synthesis (X = C, N) under Lewis acid Catalyzed Conditions

“…41 The same reactivity was also observed with TMS-1MeO-mannose to initially provide the first example of an anhydro-C-mannoside (10), which in turn could be converted to α-allyl-rhamnopyranoside 11 (74%, Scheme 5B) in a 1-pot operation. 42 Since one of the compounds identified in the unselective silylium control experiment in Scheme 4A (top) was a C-allylfuranoside, and there are few methods for C-furanoside synthesis, 43,44 we sought to optimize our protocol for these structures. This was achieved by drawing on a recent report demonstrating that B(C 6 F 5 ) 3 could catalyze the condensative cyclization of per-silylated hexopyranoses to 1,6-anhydrosugars (i.e., 12 and a mixture of 19 and 20 in Scheme 6).…”

“…Since one of the compounds identified in the unselective silylium control experiment in Scheme A (top) was a C -allyl-furanoside, and there are few methods for C -furanoside synthesis, , we sought to optimize our protocol for these structures. This was achieved by drawing on a recent report demonstrating that B­(C 6 F 5 ) 3 could catalyze the condensative cyclization of per-silylated hexopyranoses to 1,6-anhydro-sugars (i.e., 12 and a mixture of 19 and 20 in Scheme ).…”

Regioselective Dehydration of Sugar Thioacetals under Mild Conditions

“…Using L-arabinose, which is available from waste sugar-beet pulp, 15,16 as a test substrate, the corresponding ethyl-and phenyl thioacetals were prepared via reported procedures. 17,18 Treatment of the ethyl thioacetal with K2CO3/dimethyl carbonate (DMC) led to the formation of a complex mixture of products.…”

“…syn-4 and anti-4) under very mild conditions. 14,15 These reactions are readily scalable and provided access to useful chiral building blocks in only a few steps. Importantly, it was also observed that cyclisation of the sugar hydrazones under acidic or basic conditions provided complementary stereoselectivities.…”

Regioselective Dehydration of Sugar Thioacetals under Mild Conditions

“…Using l -arabinose, which is available from waste sugar beet pulp, 15 , 16 as a test substrate, the corresponding ethyl and phenyl thioacetals were prepared via the reported procedures. 17 , 18 Treatment of the ethyl thioacetal with K 2 CO 3 /dimethyl carbonate (DMC) led to the formation of a complex mixture of products.…”