Enantioselective Synthesis of α− and β−Boc‐protected 6‐Hydroxy‐pyranones: Carbohydrate Building Blocks

Abstract

As part of a larger effort aimed at using the tools of asymmetric synthesis for medicinal chemistry, chemists have been seeking new methods for the de novo asymmetric synthesis of carbohydrates. One broadly applicable asymmetric approach involves the use of α‐ and β‐6‐t‐butoxycarboxy‐2H‐pyran‐3(6H)‐ones as carbohydrate precursors. This article describes the enantioselective synthesis of α‐ and β‐Boc protected 6‐hydroxy‐pyranones.

Boc-Pyranones as building block towards biologically important Oligosaccharide Natural Products

“…This approach makes use of masked enone as an atom-less protecting group and only one protection (-AcCl) was used throughout the synthesis of mezzettiasides. 3 Retrosynthetically, both tetrasaccharides (mezzettiaside- [5][6][7] and trisaccharides (mezzettiaside-2-4&8) could be obtained from a common trisaccharide enone precursor (5a). The trisaccharide intermediate 5a was obtained from protected disaccharide intermediate 3funder Pd-catalyzed glycosylation with Boc-Pyranone (1.3).…”

“…These natural products were isolated from Cleistopholis patens/glauca and some are known to possess antimicrobial activity against methicillin-resistant Staphylococcus aureus, while others possess anti-cancer activity. [8][9][10][11] Utilizing asymmetric divergent approach, the synthesis of all the 8 highly complex natural products was completed using only two protecting groups starting from Boc-Pyranone 1.3 [5][6][7] . Once again, the pyranone has shown its wide application towards the synthesis of oligosaccharides.…”

“…[1][2][3][4] In particular, Bocprotected pyranones act an precursor or building blocks towards the synthesis of variety of the natural/unnatural products containing carbohydrate motifs (e.g., mezzettiasides, Cleistriosides/Cleistetrosides). [5][6][7][8] The unique feature of this methodology is the conversion of achiral 2-acetyl furan (1) to chiral products using asymmetric catalysis and the concept is termed as De Novo approach to carbohydrates. This de novo approach installs the desired functionality and chirality in the sugar from achiral framework.…”

“…2-acetyl furan upon treatment with Noyori (S,S) catalyst in presence of HCOONa (hydrogen source) provided the corresponding furan alcohol (1.1) with 'S' configuration. Alcohol (1.1) further underwent Achmatowicz oxidative rearrangement (NBS/NaOAc/H 2 O) [5][6][7][17][18][19][20][21][22][23][24] to provide an inseparable mixture of hemiacetal (1.2) followed by hydroxyl protection using (Boc) 2 O/DMAP at -78 o C to provide the corresponding -L-Boc-Pyranone (1.3) and -L-Boc-Pyranone (1.4) in ~3:1 ratio (55-60% over 3 steps, Scheme 1). The Boc-protected pyranones act as a glycosyl donor under typical Pd-catalyzed glycosylation reaction conditions and reacts readily with glycosyl acceptor in various solvents (e.g., CH 2 Cl 2 , THF).…”

“…3 In this regard, the diol (2d) on treatment with Pyranone 1.3 in presence of boron catalyst under palladium glycosylation conditions (30 mol% Ph 2 BOCH 2 CH 2 NH 2 / 2.5 mol% Pd PPh 3 ) 2, a good C-3:C-2 (7.5:1) regioselectivity and complete control of stereoselectivity was obtained. 3,6,13 Although the regiomers (3a/3b) were inseparable but were carried forward as it. Further, the mixture of enones (3a/3b) was protected as chloroacetate ((ClAc) 2 O/pyridine) providing again an inseperable mixture of C-3:C-2 (3c/3d) followed by treatment with NaBH 4 /CeCl 3 provided pure disaccharide allylic alcohol 3e using column chromatography with excellent yield (Scheme 3).…”