chapter  15
Pyranose-Fused Butenolides: An Expedient Preparation from Furanose Synthons
Pages 22

Experimental Methods ........................................................................................... 140 General Methods ............................................................................................... 140

1,2:5,6-Di-O-Isopropylidene-α-d-Ribo-Hexofuranosid-3-Ulose (1) ........... 141 3-Deoxy-3-C-[(Z)-(Ethoxycarbonyl)methylene]- 1,2:5,6-Di-O-Isopropylidene-α-d-Ribo-Hexofuranose (2) and 3-Deoxy-3-C-[(E)-(Ethoxycarbonyl)methylene]-1,2:5,6-Di-OIsopropylidene-α-d-Ribo-Hexofuranose (3) ................................................. 141 3-C-(Carboxymethylene)-3-Deoxy-d-Ribo-Hexopyranose3′,2-Lactone (4) ............................................................................................ 141 3-Deoxy-3-C-[(Z)-(Ethoxycarbonyl)methylene]-1,2-O-Isopropylideneα-d-Ribo-Hexofuranose (5) .......................................................................... 142 3-Deoxy-3-C-[(Z)-(Ethoxycarbonyl)methylene]-1,2-OIsopropylidene-6-O-Pivaloyl-α-d-Ribo-Hexofuranose (6) and 3-Deoxy-3-C-[(Z)-(Ethoxycarbonyl)methylene]-1,2-O-Isopropylidene5,6-Di-O-Pivaloyl-α-d-Ribo-Hexofuranose (7) ............................................ 142 3-C-(Carboxymethylene)-3-Deoxy-6-O-Pivaloyl-d-RiboHexopyranose-3′,2-Lactone (8) .................................................................... 143 1,4,6-Tri-O-Acetyl-3-C-(Carboxymethylene)-3-Deoxy-d-RiboHexopyranose-3′,2-Lactone (9) .................................................................... 143 5-O-Tert-Butyldimethylsilyl-1,2-O-Isopropylidene-α-d-ErythroPentofuranos-3-Ulose (10) ........................................................................... 144

The α,β-unsaturated γ-lactone moiety, that is, butenolide and α-methylene-γ-lactone, represents an essential fragment in numerous bioactive compounds, including natural products.1 Their conjugated carbonyl system, which is prone to nucleophilic attack by enzymes’ nucleophiles, especially by Michael addition, frequently determines their bioactivity.2 Because of a wide variety of their biological properties, including cytotoxic3 and antimicrobial activities,4 much progress has been made in the development of synthetic approaches toward such structural motifs.5 Particularly, the insertion of α,β-unsaturated γ-lactone in sugar scaffolds has provided access to a series of bicyclic compounds exhibiting signi¥cant antifungal properties6 and potent and selective insecticidal activity.7 Therefore, sugar derivatives containing α,βunsaturated γ-lactones are potential targets for the synthesis of sugar-based bioactive substances and valuable precursors for further derivatization, taking advantage of the ability of the conjugated system to undergo a variety of reactions.8 Examples of pyranose-fused butenolides include intermediates for important sugar derivatives,

5-O-Tert-Butyldimethylsilyl-3-Deoxy-3-C-[(Z)-(Ethoxycarbonyl) methylene]-1,2-O-Isopropylidene-α-d-Erythro-Pentofuranose (11) and 5-O-Tert-Butyldimethylsilyl-3-Deoxy-3-C-[(E)-(Ethoxycarbonyl) methylene]-1,2-O-Isopropylidene-α-d-Erythro-Pentofuranose (12) ............ 144 3-C-(Carboxymethylene)-3-Deoxy-d-Erythro-Pentopyranose-3′,2Lactone (13) ................................................................................................. 145

Acknowledgment ................................................................................................... 145 References .............................................................................................................. 157

such as the mycotoxin patulin,9 or a 2-C-branched-chain sugar.10 Their synthesis involved pyran-2-uloses as precursors, which are generally obtained in low yield by chemical synthesis. Our research group used this type of compounds for the synthesis of the sugar moiety of miharamycins.11 This antibiotic is a potent inhibitor of Pyricularia oryzae, which causes the rice blast disease and is also considered a potential biological weapon. A prerequisite for ef¥cient transformation into other analogues requires easy access to bicyclic structures comprising pyranose-fused ¥ve-membered ring lactones. In view of the synthetic utility and the biological pro-¥le of α,β-unsaturated γ-lactones, we report herein a full experimental procedure for an ef¥cient and stereoselective access to pyranose-fused butenolides, starting from readily available furanos-3-uloses. The methodology is based on the stereoselective Wittig ole¥nation of 1,2-O-isopropylidene-α-d-pento-or -hexofuranos-3uloses containing acid-labile protecting groups. The subsequent acid hydrolysis of the intermediate (Z)-α,β-unsaturated esters allows intramolecular transesteri¥cation and furanose−pyranose isomerization, resulting in ready formation of the bicyclic fused butenolide−pyranose system.