Synthesis of (Z)-3,7-anhydro-1,2-dideoxy-2-deuterio-D-gluco-oct-2- enitol, a prochiral substrate for probing the catalytic functioning of of glucosylases

Synthesis of the title compound provides a prochiral, glycosyl-donor substrate well suited for use as a probe of the catalytic functioning of D-glucosyl-mobilizing enzymes, because the full stereochemistry of enzymic reactions at its double bond may be unambiguously determined by examining the reaction products. The starting material for the synthesis was 2,6-anhydro-D-glycero-D-gulo-heptonic acid, from which 3,7-anhydro-4,5,6,8-tetra-O-benzyl-1-deoxy-D-glycero-D-gulo-2- octulose was prepared in eight steps. Reduction with lithium aluminum deuteride, and conversion of the resulting diastereomeric alcohols into (Z)-3,7-anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-2-deuterio-D- gluco-oct-2-enitol (11) and 3,7-anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-2-deuterio-D- glycero-D-gulo-oct-1-enitol (16), was carried out. By-products were 3,7-anhydro-2-O-benzoyl-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-2-deuterio -D-erythro-L-galacto-octitol and 3,7-anhydro-2-O-benzoyl-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-2-deuterio -D-erythro-L-talo-octitol, which could, like compound 16, be recycled. On debenzylation the oct-2-enitol 11 yielded (Z)-3,7-anhydro-1,2-dideoxy-2-deuterio-D-gluco-oct-2-enitol.     

Stereochemistry of D-galactal and D-galacto-octenitol hydration by coffee bean alpha-galactosidase: insight into catalytic functioning of the enzyme.

Green coffee bean alpha-galactosidase was found to catalyze the hydration of D-galactal and (Z)-3,7-anhydro-1,2-dideoxy-D-galacto-oct-2-enitol (D-galacto-octenitol), each a known substrate for beta-galactosidase. The hydration of D-galactal by the alpha-galactosidase in D2O yielded 2-deoxy-2(S)-D-[2-2H]galactose; the hydration of D-[2-2H]galacto-octenitol in H2O yielded 1,2-dideoxy-2(R)-D-[2-2H]galactooct-3-ulose. Thus, the enzyme protonated each substrate from beneath the plane of the ring, as assumed for alpha-D-galactosides. These results provide an unequivocal assignment of the orientation of an acidic catalytic group to the alpha-galactosidase reaction center. In addition, they reveal a pattern of glycal/exocyclic enitol/glycoside protonation by the enzyme that differs from the pattern reported for beta-galactosidase and from that reported for alpha-glucosidases. Further findings show that D-galacto-octenitol is hydrated by the coffee bean alpha-galactosidase to form the alpha-anomer of 1,2-dideoxy-D-galactooctulose and by Escherichia coli beta-galactosidase to form the beta-anomer. That each enzyme converts this enolic substrate to a product whose de novo anomeric configuration matches that formed from its D-galactosidic substrates provides new evidence for the role of protein structure in controlling the steric outcome of reactions catalyzed by these and other glycosylases. The findings are discussed in light of the concept that catalysis by glycosidases involves a "plastic" protonation phase and a "conserved" product configuration phase.     

Palladium-Mediated Coupling Reactions of an Aminosubstituted Heterocycle. Direct Synthesis of C-Nucleosides Related to Adenosine

Abstract

C-Nucleosides of the pyrazolo[1, 5-a]-1, 3, 5-triazine aglycon system have been prepared by palladium-mediated coupling of 8-iodopyrazolo[1, 5-a]-1, 3, 5-triazines. 4-(N, N-Diisobutyloxycarbonyl)amino-8-iodopyrazolo[1, 5-a]-1, 3, 5-triazine and the furanoid glycal 1, 4-anhydro-2-deoxy-3-O[(1, 1 dimethylethyl)diphenylsilyl]-D-erythro-pent-1-enitol coupled in the presence of catalytic palladium(0) to yield, after desilylation of the intermediate silyl enol ether, a C-glycoside analog of adenosine.     

Syntheses and reactions of 5-O-acetyl-1,2-anhydro-3-O-benzyl-alpha-D-ribofuranose and beta-D-lyxofuranose, 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl- and 1,2-anhydro-5,6-di-O-benzoyl-3-O-benzyl-beta-D-mannofuranose, and 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-alpha-D-glucopyranose and -beta-D-talopyranose

The title compounds 5-O-acetyl-1,2-anhydro-3-O-benzyl-alpha-D-ribofuranose and 5-O-acetyl-1,2-anhydro-3-O-benzyl-beta-D-lyxofuranose, and 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-alpha-D-glucopyranose and 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-beta-D-talopyranose, and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta-D-mannofuranose and 1,2-anhydro-5,6-di-O-benzoyl-3-O-benzyl-beta-D-mannofuranose have each been synthesized from the corresponding 2-O-tosylate and 1-free hydroxyl intermediates by base-initiated intramolecular S(N)2 ring closure in almost quantitative yields. Acetyl and benzoyl groups were not affected in the ring closure reactions. Condensation of 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-alpha-D-glucopyranose and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta-D-mannofuranose with 1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose in the presence of ZnCl2 as the catalyst afforded the 1,2-trans-linked 6-O-acetyl-3,4-di-O-benzyl-beta-D-glucopyranosyl-(1-->6)-1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose and 5-O-acetyl-3,6-di-O-benzyl-alpha-D-mannofuranosyl-(1-->6)-1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose as the sole products in satisfactory yields, while condensation of 5-O-acetyl-1,2-anhydro-3-O-benzyl-beta-D-lyxofuranose with 3-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose yielded the 1,2-trans-linked 5-O-acetyl-3-O-benzyl-alpha-D-lyxofuranosyl-(1-->5)-3-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose as the sole product in a good yield. The 6-O-acetyl group in the glycosyl donor, 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl-alpha-D-glucopyranose, did not influence the stereoselectivity of the ring-opening-coupling reaction.     

Analysis of linkage positions in a polysaccharide containing nonreducing, terminal alpha-D-glucopyranosyluronic groups by the reductive-cleavage method

The fate of terminal (nonreducing) alpha-D-glucopyranosyluronic groups under reductive cleavage conditions was investigated by using the Klebsiella K2 (strain NCTC-418) capsular polysaccharide. Treatment of the fully methylated polysaccharide (1) with triethylsilane and a mixture of trimethylsilyl methanesulfonate (Me3SiOSO2CH3) and boron trifluoride etherate (BF3.Et2O) as the catalyst, resulted in complete cleavage of all glycosidic linkages to yield the expected products, namely 3-O-acetyl-1,5-anhydro-2,4,6-tri-O-methyl-D-glucitol (2), 3,4-di-O-acetyl-1,5-anhydro-2,6-di-O-methyl-D-mannitol (3), 4-O-acetyl-1,5-anhydro-2,3,6-tri-O-methyl-D-glucitol (4), and methyl 2,6-anhydro-3,4,5-tri-O-methyl-L-gulonate. Treatment of 1 with trimethylsilyl trifluoromethanesulfonate (Me3SiOSO2CF3) as the catalyst resulted in incomplete cleavage of the glycosidic linkage of the methylated D-glucopyranosyluronic group, to yield 4-O-acetyl-1,5-anhydro-2,6-di-O-methyl- 3-O-(methyl2,3,4-tri-O-methyl-alpha-D-glucopyranosyluronate )-D-mannitol (9). Reductive cleavage of 1 in the presence of BF3.Et2O resulted in incomplete cleavage of all glycosidic linkages and gave rise to all four dimers (including 9) that could be formed from a tetrasaccharide repeating unit. The proposed structures of these dimers are based upon their composition, as established by chemical ionization mass spectrometry and by the reported structure of the polysaccharide. A small proportion of 1,5-anhydro-2,4,6-tri-O-methyl-3-O-(methyl 2,3,4-tri-O-methyl-alpha-D-glucopyranosyluronate)-D-mannitol (12) was also detected in the products of the BF3.Et2O-catalyzed reductive cleavage. The presence of 12 is chemical evidence for the phase of the tetrasaccharide repeating unit in the polysaccharide. The reductive cleavage of 1 was also accomplished after reduction of its ester groups with lithium aluminum hydride. Complete cleavage of all glycosidic linkages was observed when either Me3SiOSO2CF3 or Me3SiOSO2CH3-BF3.Et2O was used to catalyze reductive cleavage, and anhydroalditols 2, 3, 4, and 6-O-acetyl-1,5-anhydro-2,3,4-tri-O-methyl-D-glucitol were produced, as expected.     

Steric course of the hydration of D-gluco-octenitol catalyzed by alpha-glucosidases and by trehalase

Crystalline Aspergillus niger alpha-glucosidase and highly purified preparations of rice alpha-glucosidase II and Trichoderma reesei trehalase were found to catalyze the hydration of [2-(2)H]-D-gluco-octenitol, i.e., (Z)-3,7-anhydro-1,2-dideoxy-[2-2H]-D-gluco-oct-2-enitol, to yield 1,2-dideoxy-[2-2H]-D-gluco-octulose. In each case, the stereochemistry of the reaction was elucidated by examining the newly formed centers of asymmetry at C-2 and C-3 of the hydration product. The C-1 to C-3 fragment of each isolated [2-2H]-D-gluco-octulose product was recovered as [2-2H]propionic acid and identified by its positive optical rotatory dispersion as the S isomer, showing that each enzyme had protonated the octenitol (at C-2) from above its re face. 1H NMR spectra of enzyme/D-gluco-octenitol digests in D2O showed that the alpha-anomer of [2-2H]-D-gluco-octulose was exclusively produced by each alpha-glucosidase, whereas the beta-anomer was formed by action of the trehalase. The trans hydration catalyzed by the alpha-glucosidases was found to be very strongly inhibited by the substrate; the cis hydration reaction catalyzed by the trehalase showed no such inhibition. Special importance is attached to the finding that in hydrating octenitol each enzyme creates a product of the same anomeric form as in hydrolyzing an alpha-D-glucosidic substrate. This result adds substantially to the growing evidence that individual glycosylases create the configuration of their reaction products by a means that is independent of donor substrate configuration, that is, by a means other than "retaining" or "inverting" substrate configuration.     

An unsaturated peptidomimetic assembly derived from a carbohydrate.

A strategy has been established for the synthesis of peptidomimetics derived from unsaturated carbohydrates, and exemplified by the use of methyl 2,6-anhydro-7-azido-3,7-deoxy-4,5-O-isopropylidene-D-lyxo-hept-2-enonate 9 as a dipeptide 'monomer' which can be elaborated from either end. Selective reduction of 9 gives a protected pseudodipeptide ester suitable for use as an amino component, and saponification gives an azido acid suitable for use as a carboxyl component. The 'dimer' product of coupling these two components with TBTU can be similarly elaborated at either end to give a 'trimer' and a further cycle of selective reduction and coupling gave a 'tetramer', 17, a pseudo-octapeptide.     

Synthesis of methyl alpha-L-vancosaminide

The synthesis of methyl alpha-L-vancosaminide from di-O-acetyl-L-rhamnal is described. The allylic alcohol methyl 2,3,6-trideoxy-3-C-methyl-alpha-L-threo-hex-2-enopyranoside was prepared from the glycal, 1,5-anhydro-1,2,6-trideoxy-3-C-methyl-L-ribo-hex-1-enitol, and converted to its N,N-dimethylisourea derivative. The cis amino alcohol functionality in vancosamine was introduced by the electrophilic cyclization of the isourea, followed by hydrolysis of the resulting oxazoline.     

Syntheses related to the 3,7-anhydro-octose in the ezomycins and the octosyl acids

Two 3,7-anhydro-octoses, namely, methyl 3,7-anhydro-5,6,8-trideoxy-β-d-allo-octofuranoside and methyl 3,7-anhydro-5,6,8-trideoxy-α-l-talo-octofuranoside, have been synthesized. The synthetic sequence includes the preparation of an octose from d-ribose by way of a Wittig reaction and the elaboration of the bicyclic-ring system by intramolecular cyclization.     

Analysis by the reductive-cleavage method of linkage positions in a polysaccharide containing 4-linked D-glucopyranosyluronic residues

The fate of 4-linked D-glucopyranosyluronic residues under reductive-cleavage conditions was investigated by using the Klebsiella aerogenes type 54 strain A3 capsular polysaccharide. Treatment of the fully methylated polysaccharide with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane, followed by in situ acetylation, yielded 1,5-anhydro-2,3,4,6-tetra-O-methyl-D-glucitol, 3,4-di-O-acetyl-1,5-anhydro-2,6-di-O-methyl-D-glucitol, and 3-O-acetyl-1,5-anhydro-2,4-di-O-methyl-L-fucitol, as expected, but the expected product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue, namely, methyl 3-O-acetyl-2,6-anhydro-4,5-di-O-methyl-L-gulonate, was not observed. Instead, methyl 2-O-acetyl-3,6-anhydro-4,5-di-O-methyl-L-gulonate (6) was identified as the sole product of reductive cleavage of the 4-linked D-glucopyranosyluronic residue. That compound 6 arose as a result of rearrangement during reductive cleavage rather than by reductive cleavage of a 5-linked D-glucofuranosyluronic residue, was established by reductive cleavage of the fully methylated polysaccharide following reduction of its ester groups with either lithium aluminum hydride or lithium aluminum deuteride. The products of the latter reductive cleavage were the same as before, except for the absence of 6 and the presence of 4,6-di-O-acetyl-1,5-anhydro-2,3-di-O-methyl-D-glucitol, or its 6,6-dideuterio isomer. Although the reductive-cleavage technique is suitable for the direct analysis of polysaccharides containing 4-linked D-glucopyranosyluronic residues, it does not establish whether the uronic residue is a 4-linked pyranoside or a 5-linked furanoside. The expected product is, however, derived from the 4-linked D-glucopyranosyluronic residue after sequential methylation, reduction of its ester group and reductive cleavage.     

X-ray diffraction and high-resolution NMR spectroscopy of methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enopyranuronate

Single-crystal X-ray diffraction and high-resolution (1)H and (13)C NMR spectral data for methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enopyranuronate are reported. The (5)H(4) conformation was found to be the preferred form for this glycal, both in the crystal lattice and in solution. The factors determining the (4)H(5)<==>(5)H(4) conformational equilibrium for acetylated glycals are discussed.     

A new chemical synthesis of Ascopyrone P from 1,5-anhydro-D-fructose

The naturally occurring antioxidant Ascopyrone P (1,5-anhydro-4-deoxy-D-glycero-hex-1-en-3-ulose, 1) was prepared from the rare sugar 1,5-anhydro-D-fructose (AF, 3) in three steps in an overall yield of 36%. Thus, acetylation of 3 afforded the enolone 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulopyranose (4), which could be isomerised to 2,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-1-ene-3-ulose (6). Deacetylation of 6 under mild conditions gave crystalline Ascopyrone P (1).     

Denitration of carbohydrate α-nitroepoxides by nucleophiles

Several nucleophiles were separately treated with methyl and phenyl 2,3-anhydro-4,6-O-benzylidene-3-deoxy-3-nitro-β-d-allopyranoside, to give 2-substituted aldos-3-ulose derivatives. In the latter case, the subsequent β-elimination of the aglyconic phenyl group always occurred to afford the corresponding glycal. Reaction mechanisms thereof are also discussed.     

Synthesis of S-linked thiooligosaccharide analogues of Nod factors: synthesis of new protected thiodisaccharide and thiotrisaccharide intermediates

We are investigating the synthesis of thioanalogues of nodulation factors that will be resistant to degradation by chitinases. To study the influence of our protecting group strategy, the glycosylation of 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside (7) with two trichloroacetimidate glycosyl donors carrying an azido group at C-2 and either benzyl or benzoyl protecting groups on O-3 and O-4 was first attempted under catalysis with BF(3).Et(2)O in toluene. While glycosylation with the benzoylated glycosyl donor gave only a poor yield (27%) of the disaccharide, a similar reaction with the benzylated donor gave the corresponding disaccharide in good yield (77%). Although both products were obtained as anomeric mixtures, the benzylated donor led to improved stereoselectivity in favor of the desired beta-anomer (alpha:beta 3:7). Based on these results, a novel thiotrisaccharide was synthesized via the coupling of 7 with 6-O-acetyl-4-S-(3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D-glucopyranosyl)-2-azido-3-O-benzyl-2-deoxy-4-thio-alpha-D-glucopyranosyl trichloroacetimidate (25) also newly synthesized. After optimization of the reaction conditions, the desired thiotrisaccharide 4-O-[6-O-acetyl-4-S-(3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-beta-D-glucopyranosyl)-2-azido-3-O-benzyl-2-deoxy-4-thio-beta-D-glucopyranosyl]-1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside (26beta) was obtained in 57% yield. These conditions led to an anomeric mixture in favor of the desired beta-anomer (alpha:beta 1:4.7) that was separated from the alpha-anomer by normal-phase HPLC on a PrepNova Pack(R) silica gel cartridge. The work described here shows that thiodisaccharide glycosyl donors behave quite differently from the analogous O-disaccharide used previously to synthesize nodulation factors.     

Synthesis of modified tetrasaccharide sequences of N-glycoproteins

The tetrasaccharides O-alpha-D-mannopyranosyl-(1----3)-O-[alpha-D- mannopyranosyl-(1----6)]-O-(4-deoxy-beta-D-lyxo-hexopyranosyl)-(1- ---4)-2- acetamido-2-deoxy-alpha, beta-D-glycopyranose (22) and O-alpha-D-mannopyranosyl-(1----3)-O-[alpha-D-mannopyranosyl-(1----6)]-O- beta-D-talopyranosyl-(1----4)-2-acetamido-2-deoxy-alpha, beta-D- glucopyranose (37), closely related to the tetrasaccharide core structure of N-glycoproteins, were synthesized. Starting with 1,6-anhydro-2,3-di-O-isopropylidene-beta-D-mannopyranose, the glycosyl donors 3,6-di-O-acetyl-2-O-benzyl-2,4-dideoxy-alpha-D-lyxo- hexopyranosyl bromide (10) and 3,6-di-O-acetyl-2,4-di-O-benzyl-alpha-D-talopyranosyl bromide (30), were obtained in good yield. Coupling of 10 or 30 with 1,6-anhydro-2-azido-3-O-benzyl-beta-D-glucopyranose to give, respectively, the disaccharides 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(3,6-di-O-acetyl-2-O-benzyl-4 -deoxy- beta-D-lyxo-hexopyranosyl)-beta-D-glucopyranose and 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(3,6-di-O-acetyl-2,4-di-O-ben zyl- beta-D-talopyranosyl)-beta-D-glucopyranose was achieved with good selectivity by catalysis with silver silicate. Simultaneous glycosylation of OH-3' and OH-6' of the respective disaccharides with 2-O-acetyl-3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl chloride yielded tetrasaccharide derivatives, which were deblocked into the desired tetrasaccharides 22 and 37.     

The preparation of 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-,β-d-fructofuranoside and the conversion of chlorinated derivatives into anhydrides

Under carefully controlled conditions, sucrose is converted by selective reaction with sulphuryl chloride into either 6-chloro-6-deoxy-α-d-glucopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside or 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside, which could be isolated without recourse to chromatography. Treatment of the dichloride with sodium methoxide gave 3,6-anhydro-β-d-glucopyranosyl, 3,6-anhydro-β-d-fructofuranoside in high yield. In contrast, 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside gave, in two distinct stages, 3,6-anhydro-4-chloro-4-deoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside and 3,6-anhydro-4-chloro-4-deoxy-α-d-galactopyranosyl 3,6-anhydro-β-d-fructofuranoside. The structures of these products were ascertained by ¹H-n.m.r. and mass spectrometry.     

Lyase activity of nucleoside 2-deoxyribosyltransferase: transient generation of ribal and its use in the synthesis of 2'-deoxynucleosides

In the absence of acceptors nucleoside 2-deoxyribosyltransferase catalyzes the slow hydrolysis of 2'-deoxynucleosides. During this hydrolytic reaction, D-ribal (1,4-anhydro-2-deoxy-D-erythro-pent-1-enitol), a glycal of ribose hitherto encountered only as a reagent in organic synthesis, is generated spontaneously, disappearing later as 2'-deoxynucleoside hydrolysis approaches completion. Nucleoside 2-deoxyribosyltransferase is found to catalyze the hydration of D-ribal in the absence of nucleic acid bases and the synthesis of deoxyribonucleosides from ribal in their presence, affording a new method for the preparation of 2'-deoxyribonucleosides. The stereochemistry of nucleoside formation from ribal supports the intervention of deoxyribosyl-enzyme intermediate. The equilibrium constant for the covalent hydration of ribal is found to be approximately 65.     

Yield of 1,6-anhydro-3,4-dideoxy-β-d-glycero-hex-3-enopyranos-2-ulose (levoglucosenone) on the acid-catalyzed pyrolysis of cellulose and 1,6-anhydro-β-d-glucopyranose (levoglucosan)

Although 1,6-anhydro-3,4-dideoxy-,β-d-glycero-hex-3-enopyranos-2-ulose (2) is produced by the acid-catalyzed pyrolysis of both cellulose and 1,6-anhydro-β-d-glucopyranose (1), data presented here show that the principal mechanism of its formation in the pyrolysis of cellulose is not via 1. Furthermore, the data provide evidence that 1 itself is not a primary product of cellulose pyrolysis, so that the principal mechanism of its formation must involve a precursor as yet unidentified.     

Two-step regio- and stereoselective syntheses of [19F]- and [18F]-2-deoxy-2-(R)-fluoro-beta-D-allose

Replacement of specific hydroxyl groups by fluorine in carbohydrates is an ongoing challenge from chemical, biological, and pharmaceutical points of view. A rapid and efficient two-step, regio- and stereoselective synthesis of 2-deoxy-2-(R)-fluoro-beta-d-allose (2-(R)-fluoro-2-deoxy-beta-d-allose; 2-FDbetaA), a fluorinated analogue of the rare sugar, d-allose, is described. TAG (3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol or 3,4,6-tri-O-acetyl-d-glucal), was fluorinated in anhydrous HF with dilute F(2) in a Ne/He mixture or with CH(3)COOF at -60 degrees C. The fluorinated intermediate was hydrolyzed in 1N HCl and the hydrolysis product was purified by liquid chromatography and characterized by 1D (1)H, (13)C, and (19)F NMR spectroscopy as well as 2D NMR spectroscopy and mass spectrometry. In addition, (18)F-labeled 2-deoxy-2-(R)-fluoro-beta-d-allose (2-[(18)F]FDbetaA) was synthesized for the first time, with an overall decay-corrected radiochemical yield of 33+/-3% with respect to [(18)F]F(2), the highest radiochemical yield achieved to date for electrophilic fluorination of TAG. The rapid and high radiochemical yield synthesis of 2-[(18)F]FDbetaA has potential as a probe for the bioactivity of d-allose.     

Synthesis of dl-4,5,6-trinor-3,7-inter-m-phenylene-3oxaprostaglandins including one which inhibits platelet aggregation.

The synthesis of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxaprostaglandins of the E1 and F1alpha series from 6-endo-(1-heptenyl)-bicyclo[3:1:0]hexan-3-one (III), is described. Preliminary biological screening data for gerbil colon smooth muscle stimulation, rat blood pressure and substrate specificity toward 15-hydroxyprostaglandin dehydrogenase is presented. Platelet function studies, both in vitro and in vivo of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxa-PGE1, methyl ester (VIII) are presented.