103597-20-2

Upstream product

• 127214-37-3 (2S,3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-2-methoxy-6-vinyl-tetrahydro-pyran 
• 174155-13-6 methyl 6-deoxy-2,3,4-tri-O-benzyl-α-D-gluco-hepto-1,7-dialdopyranoside 
• 1049006-96-3 C₅₉H₆₆O₁₁ 
• 103597-19-9 methyl 2,3,4-tri-O-benzyl-6,7-dideoxy-D-glycero-α-D-glucooct-7-eno-1,5-pyranoside 
• 103597-18-8 methyl-2,3,4-tri-O-benzyl-7,7,8,8-tetradehydro-7,8-dideoxy-α-D-glycero-D-gluco-octopyranoside 
• 155020-87-4 methyl (6R)-2,3,4-tri-O-benzyl-6-(2-thiazolyl)-α-D-glucopyranoside 
• 34212-64-1 methyl 2,3,4-tri-O-benzyl-α-D-mannopyranoside 
• 40653-15-4 methyl 2,3,4-tri-O-benzyl-α-D-manno-hexodialdo-1,5-pyranoside 
• 117192-23-1 3-O-benzyl-5-deoxy-1,2-O-isopropylidene-5-C--α-D-xylofuranose 
• 220172-62-3 (E)-3-((3aR,5R,5aS,8aS,8bR)-2,2,7,7-Tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4',5'-d]pyran-5-yl)-1-((2S,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-propenone 
• 220172-57-6 (E)-3-((4S,5R,4'R)-2,2,2',2'-Tetramethyl-[4,4']bi[[1,3]dioxolanyl]-5-yl)-1-((2S,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-propenone 
• 220172-55-4 dimethyl (methyl 2,3,4-tri-O-benzyl-D-gluco-heptopyranos-6-ulos-7-yl)phosphonate 
• 120403-24-9 (methyl 2,3,4-tri-O-benzyl-α-D-glucopyranosiduronyl)-(triphenylphosphoranylidene)methane 
• 55610-71-4 methyl (methyl-2,3,4-tri-O-benzyl-α-D-glucopyranosid)uronate 

Downstream Products

• 103597-32-6 (R)-1-((2R,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-2-trityloxy-ethanol 
• 155154-54-4 methyl D-glycero-α-D-gluco-heptopyranoside 
• 103597-27-9 Methanesulfonic acid (R)-2-hydroxy-1-((2S,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-ethyl ester 
• 103597-30-4 Acetic acid (S)-2-azido-2-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-ethyl ester 
• 103597-28-0 Acetic acid (R)-2-methanesulfonyloxy-2-((2S,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-ethyl ester 
• 103597-29-1 (2R,3R,4S,5R,6S)-2-((S)-1-Azido-2-trityloxy-ethyl)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran 
• 103597-26-8 Methanesulfonic acid (R)-1-((2S,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-2-trityloxy-ethyl ester 
• 103597-31-5 Benzoic acid (S)-1-((2R,3S,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-2-trityloxy-ethyl ester 
• 103597-32-6 (S)-1-((2R,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-2-trityloxy-ethanol 
• 103597-24-6 methyl 2,3,4-tri-O-benzyl-L-glycero-α-D-gluco-heptopyranoside 
• 103597-25-7 methyl 6,7-di-O-acetyl-2,3,4-tri-O-benzyl-L-glycero-α-D-gluco-heptopyranoside 
• 155021-04-8 methyl 4,6-O-benzylidene-3-O-methyl-D-glycero-α-D-altro-heptopyranoside 
• 155021-02-6 methyl 4,6-O-benzylidene-D-glycero-α-D-altro-heptopyranoside 
• 155021-01-5 2,3-anhydro-4,6-O-benzylidene-D-glycero-α-D-manno-heptopyranoside 

Relevant academic research and scientific papers

β-Selective one-pot fluorophosphorylation of d,d -heptosylglycals mediated by selectfluor

This study describes the development of a novel procedure of glycal fluorophosphorylation applied to the synthesis of a fluorinated analogue of an important bacterial metabolite. This procedure was applied to several heptose-derived glycals, and the stereochemical outcome of the reaction was analyzed. Under optimized conditions, the reaction is β-gluco selective, but a significant amount of the α-gluco diastereomer is also generated.

General Homologation Strategy for Synthesis of l -glycero- and d -glycero-Heptopyranoses

A general and stereospecific homologation strategy for the synthesis of heptopyranosides is reported. The strategy employs the Wittig olefination and proline-catalyzed α-aminoxylation to achieve one carbon elongation and stereoselective hydroxylation at the C6 position, respectively. The l-glycero- and d-glycero-heptopyranosides can be obtained with nearly perfect stereoselectivity. Further study reveals the difference in the chemical shift of the C6 proton of l/d-glycero-heptopyranosyl diastereomers, which is found to be useful for assignment of the configuration of heptopyranosides.

NEW HEPTOSE DERIVATIVES AND BIOLOGICAL APPLICATIONS THEREOF

Compounds having the general formula (I) and their biological applications.

Systematic synthesis of inhibitors of the two first enzymes of the bacterial heptose biosynthetic pathway: Towards antivirulence molecules targeting lipopolysaccharide biosynthesis

L-Heptoses (L-glycero-D-manno-heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D-glycero-D-manno-heptopyranose 7-phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1-, 2-, 6- and 7-positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6- and 7- positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D-glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC50=34 μM) and HldE (IC50=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence. Copyright

The synthesis of higher carbon sugars: A study on the rearrangement of higher sugar allylic alcohols

The C12 higher sugar enone 15 (prepared from the corresponding phosphonate and aldehyde) was highly stereoselectively reduced to the d-glycero-allylic alcohol. The epimeric l-glycero-isomer was obtained by the non-selective reduction of the higher enone under Luche conditions. The separate treatment of both allylic alcohols with triflic anhydride provided the corresponding triflates, which in situ underwent allylic rearrangement with the elimination of one of the benzyl groups (from the aldehyde part of the molecule). The stereochemical aspects of this transformation are also discussed.

Stereoselective glycal fluorophosphorylation: Synthesis of ADP-2-fluoroheptose, an inhibitor of the LPS Biosynthesis

Heptosides are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP-L-glycero-β-D-manno-heptopyranose, the donor substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of this carbohydrate into LPS. Synthetically, the key step for the preparation of ADP-2F-heptose is the simultaneous and stereoselective installation of both the fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor-mediated (selectfluor= 1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2] octane bis(triflate)) electrophilic addition/nucleophilic substitution involving a heptosylglycal. Therefore, we detail in this article 1) the stereoselective preparation of the key intermediates heptosylglycals, 2) the development of a new fluorophosphorylation procedure allowing an excellent β-gluco stereoselectivity with "all-equatorial" glycals, 3) the synthesis of the target ADP-2F-heptose, and 4) some comments on the contacts observed between the fluorine atom of the final molecule and the protein in the crystallographic structure of heptosyltransferase WaaC.

Synthesis of higher carbon sugars. Unexpected rearrangement of higher sugar allylic alcohols

Coupling of a sugar phosphonate with a sugar aldehyde afforded a C13-higher sugar enone. Reduction of the carbonyl function provided both stereoisomeric allylic alcohols. Inversion of the configuration at the carbinol centre in these derivatives did not yield the expected SN2 product, but proceeded with rearrangement to the tetrahydrofuran derivative.

METHODS FOR PREPARING ENZYMATIC SUBSTRATE ANALOGS USEFUL AS INHIBITORS OF BACTERIAL HEPTOSYL-TRANSFERASES AND BIOLOGICAL APPLICATIONS OF THE INHIBITORS

The invention relates to a method for making osyl and hexoses derivatives of formula (1), especially 2-fluoro-2-deoxy derivatives, wherein R is a nucleoside such as adenosine, cytidine, guanosine, uridine and deoxy analogs such as 2-deoxy, X represents OH, halogen, particularly F, NH2, Y represents H, CH2OH, CH2NH2, CH2OPO3, CH2OSO3, Z represents O or S, and W represents O,NH, or CH2, said method comprising the steps of: a) stereoselective fluorophosphorylation of tetrapivaleate 8 to give β-gluco-type fluorophosphate, b) hydrogenation and deprotection to give a monophosphate, c) coupling said glycal with (R)P-morpholidate to give crude sugar nucleotide 1, or . alternatively, d)deacetylation then silylation of heptoglycal 7 to give tetrasilylated glycal, e)fluorophosphorylation of said glycal to give β-gluco type fluorophosphate, f) deprotection of the fluorophosphate and coupling radical R to give 1. Use of said derivatives as inhibitors of highly virulent proteins of pathogenic bacteria.

Homologation of protected hexoses with Grignard C1 reagents

Derivatives of three stereoisomeric hexodialdo-1,5-pyranosides were reacted with four Grignard C1 reagents: methoxymethyl-, allyloxymethyl-, benzyloxymethyl, and dimethylphenylsilylmethyl-magnesium chlorides. Two stereoisomeric heptoses were obtained in each case in a good yield. The methyl alloside-derived heptosides were accompanied by C-5 inverted products. The addition of Grignard reagents to aldehydes 5-8 has been discussed in terms of parallel α- or β-chelated and Felkin-Anh transition states. It has been found that the silyl Grignard reagent 12 exhibits a strong preference for the formation of heptose derivatives of L-configuration at C-6. (C) 2000 Elsevier Science Ltd.

Phosphonate versus phosphorane method in the synthesis of higher carbon sugars. Preparation of D-erythro-L-manno-D-glucododecitol

Higher sugar (C12 and C13) dialdose precursors 5, 10 and 15 were obtained by a coupling of C7-phosphorane 1 or C7-phosphonates 2 and 13 with C5- or C6-sugar aldehydes. These compounds were converted into higher dialdoses by (i) stereoselective reduction of a carbonyl group with zinc borohydride followed by (ii) osmylation of the resulting allylic alcohols. One of these derivatives - compound 8a - was converted into D-erythro-L-manno-D-gluco-dodecitol 23 on a 0.5 g scale.