6‐Deoxyhexoses from l‐Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

Abstract

In the search for alternative non-metabolizable inducers in the L-rhamnose promoter system, the synthesis of fifteen 6-deoxyhexoses from L-rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3-acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6-deoxy-D-allose, 6-deoxy-D-gulose and 6-deoxy-L-talose. Highly crystalline 3,5-benzylidene rhamnonolactone gives easy access to Lquinovose [6-deoxy-L-glucose], L-olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2-deoxy-2-fluoro-Lrhamnose and 2-deoxy-2-fluoro-L-quinovose. Biotechnology provides access to 6-deoxy-L-altrose and 1-deoxy-L-fructose.

Hanessian-Hullar reaction in the synthesis of highly substituted trans-3,4-dihydroxypyrrolidines: Rhamnulose iminosugar mimics inhibit α-glucosidase

“…As previously described, 12 the stable triflate 16, formed in 95% yield from 6, with sodium azide in DMF at -40 °C formed the kinetic glucono-azide 8 (75%) but at room temperature gave the thermodynamic mannonoazide 9 (85%); the initially formed 8 was equilibrated to the more stable all cis-azide 9. For the synthesis of the idono-and gulono-azides 10 and 11, the starting material 6-deoxy-Dgulonolactone 18 was prepared from the triacetonide 17 in 61% yield with no chromatography required; the route 13 is far more convenient than procedures from L-rhamnose 12 or Dgulonolactone (Scheme 3). 14 Reaction of 18 with benzaldehyde in the presence of concentrated hydrochloric acid gave the crystalline lactone 7 (92%) in which the methyl group is equatorial.…”

“…For the rhamnonolactones 8 and 9, the benzylidene derivative 6 can readily be obtained from rhamnose in a one pot sequence on a 50 g scale 11 [Scheme 2]. As previously described, 12 the stable triflate 16, formed in 95% yield from 6, with sodium azide in DMF at -40 °C formed the kinetic glucono-azide 8 (75%) but at room temperature gave the thermodynamic mannonoazide 9 (85%); the initially formed 8 was equilibrated to the more stable all cis-azide 9. For the synthesis of the idono-and gulono-azides 10 and 11, the starting material 6-deoxy-Dgulonolactone 18 was prepared from the triacetonide 17 in 61% yield with no chromatography required; the route 13 is far more convenient than procedures from L-rhamnose 12 or Dgulonolactone (Scheme 3).…”

“…Concentrated hydrochloride acid (37%, 4 mL) was added to a suspension of 6-deoxy-D-gulono-1,4lactone 18 12 (887 mg, 5.5 mmol) in benzaldehyde (15 mL). The reaction mixture was stirred at room temperature for 15 h during which time a solid product separated.…”

Triacetonide of Glucoheptonic Acid in the Scalable Syntheses of d-Gulose, 6-Deoxy-d-gulose, l-Glucose, 6-Deoxy-l-glucose, and Related Sugars

“…Cleavage of diol 29 with sodium periodate on silica gel in dichloromethane 17 formed aldehyde 30 (93%) which on acid ion exchange resin hydrolysis gave the deoxyhexose 31 (67%), identical to a sample produced from Lrhamnose. 7 Reduction of aldehyde 30 by sodium borohydride in methanol gave the diacetonide 32 (85%) which on removal of the acetonide protecting groups by acid hydrolysis formed 6-deoxyalditol 33 (100%). 6-Deoxy-L-glucose 31 and 6deoxy-L-glucitol 33 were formed in overall yields of 19% and 24%, respectively, from the heptonate triacetonide 2 without the need for any chromatography.…”

“…22 L-Rhamnose, a cheap 6-deoxyhexose, provides an alternative strategy for the synthesis of many of its diastereomers and derivatives. 7,23 In particular, microbial oxidations of alditols to ketoses usually give high yield regioselective reactions to a pure ketose; the 6-deoxyalditols 19 and 33 are useful starting materials for the biotechnology of Izumoring in the synthesis of deoxyhexoses. 24…”