摘要:

Earlier work in this laboratory has shown the intact incorporation of [1-13C]hexanoate into averufin (1), a key intermediate in aflatoxin B1biosynthesis. Parallel experiments with equimolar amounts of [1-13C]butyrate, [1-13C]-3-oxo-octanoate, and [1-13C]-5-oxo-hexanoate gave no detectable specific incorporation of heavy isotope but low and equivalent background incorporation comparable to [1-13C]acetate. Three of these potential intermediates in polyketide formation were reexamined as their correspondingN-acetylcysteamine (NAC) thioesters. The NAC thioester of [1-13C]hexanoic acid gave a remarkably high 22% intact incorporation while the NAC thioester of [1-13C]-3-oxo-octanoic acid afforded nearly 5% when an equimolar amount was administered to the producing organismAspergillusparasiticus(ATCC 24551). In contrast, the NAC thioester of [1-13C]butyric acid showed no selective enrichment of averufin. This negative result was tested further in a more sensitive experiment with the NAC thioester of [2,3-13C2]butyric acid. No1JCCcoupling was detectable, indicating an incorporation efficiency of <0.1%. [1-13C,18O2]Hexanoate was prepared and gave a 53% retention of18O relative to theI3C internal standard in keeping with previous experiments with [1-13C,18O2]acetate. It is concluded from these data that the initial C6segment of polyketide biosynthesis is unlikely to arise by β-oxidation of a higher fatty acid but more probably is generated by a specialized fatty acid synthase (FAS) that provides this unit either separately to the polyketide synthase (PKS) or as part of a larger FAS/PKS fusion. While these two physical arrangements cannot be distinguished by these experiments, both must accommodate comparatively efficient exchange of the NAC thioesters of both hexanoic and 3-oxo-octanoic acid, but not the NAC thioester of butyric acid.

ISSN:0008-4042    

DOI:10.1139/v94-031

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

The 1-(3-thianyl)uracil (9) and 9-(3-thianyl)adenine (14) nucleoside analogs have been prepared from the key intermediate, (±)-(3β,5β)-3-amino-5-(hydroxymethyl)thiane (6). Analog9was converted into a mixture of diastereomeric sulfoxides (10) that afforded, by a Pummerer reaction, a mixture of (±)-1-{(2′β,3′β,,5′β)-2′-acetoxy-5′-(acetoxymethyl)thian-3′-yl}-2,4(1H,3H)-pyrimidinedione (11a) and its 6′-β isomer (11b). The EI mass spectra of the nucleoside analogs are discussed. The uracil nucleoside analogs have been evaluated also for their anti-HIV and antitumor activities.

ISSN:0008-4042    

DOI:10.1139/v94-032

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

It was demonstrated that the attack of Grignard reagents such as methyl-, allyl-, and 3,3-dimethoxypropyl magnesium bromides on 11,12-dehydrocytisine occurs on the α-face, to give the corresponding 11α-alkylcytisine. (−)-Camoensine and (−)-camoensidine were synthesized from (−)-cytisine via the Grignard reaction. The absolute stereochemistry of the above alkaloids was confirmed to be 7R, 9R, 11Rand 6S, 7R, 9R, 11R, respectively.

ISSN:0008-4042    

DOI:10.1139/v94-033

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

To elucidate the reactivity of super-electrophiles such as 4,6-dinitrobenzofuroxan as compared to normal electrophiles such as 1,3,5-trinitrobenzene, reaction of isopropoxide ion (iPrO−) with a series of ambident super-electrophiles was studied by 400 MHz1H nuclear magnetic resonance spectroscopy. The 2-(nitroaryl)-4,6-dinitrobenzotriazole 1-oxides,1–3, possess both a super-electrophilic (C-7) site and a normal electrophilic (C-1′) site. Nucleophiles can demonstrate selectivity for attack at C-7, which leads to formation of persistent anionic σ-adducts (Meisenheimer complexes), as compared to C-1′, which leads to N-2:C-1′ bond scission. The most reactive substrate, 2-(2′,4′,6′-trinitrophenyl)-4,6-dinitrobenzotriazole 1-oxide (Pi-DNBT,1) was found to be the least selective substrate in C-7 adduct formation, while 2-(2′,4′-dinitrophenyl)- and 2-(4′-nitrophenyl)-4,6-dinitrobenzotriazole 1-oxides (DNP-DNBT,2, and NP-DNBT,3, respectively) showed increasing selectivity towards iPrO−, in turn. These results are discussed on the basis of overall selectivity for C-7 adduct formation and the relative selectivity of iPrO−as compared to methoxide andtert-butoxide ions. The conclusions are illustrated using comparative energy profiles. In terms of pathways for decomposition of the adducts, the C-7 adducts decompose via dissociation back to substrate and nucleophile and, thence, through C-1′ adduct formation to the scission products. However, for1, the C-7 adduct1ahas now been found to decompose to 7-isopropyl-2-picryldinitrobenzotriazole,1c. The possible mechanism of this formal internal redox will be discussed.

ISSN:0008-4042    

DOI:10.1139/v94-034

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

The total synthesis of the naturally occurring fluorenone, dengibsinin (7a), and the azafluoranthene alkaloid, imeluteine (30e), is described. Using combinedorthometalation – cross coupling sequences that terminate in Friedel–Crafts (18b → 6d) and remote metalation (21a,b → 6c,d) reactions, the synthesis of fluorenone dimethyl ethers6cand6dis reported.6cand6dwere shown not to be identical to dengibsinin dimethyl ether and dengibsin dimethyl ether, respectively, derived from the natural products. This work, together with synthetic and structural evidence from Sargent and Talapatra, led to the reassignment of structures for dengibsinin (7a) and dengibsin (7b). Using the metalation – cross coupling approach, the synthesis of the reassigned dengibsinin (7a) is presented. Two alternate unsuccessful approaches to imeluteine are briefly described (31 + 32and33 + 34). The successful approach incorporates the remote metalation – double cyclization,43 → 44, as the key step.

ISSN:0008-4042    

DOI:10.1139/v94-035

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

An exploration of the synthesis ofD-glycero-D-altro-heptose, a constitutent of O antigen chains in lipopolysaccharides fromCampylobacterjejuniserotypes O:23 and O:36 led to a study of the 2-trimethylsilylthiazole homologation procedure for heptose synthesis. In contrast to the diastereoselective formation of a 1,2:3,4-di-O-isopropylidene-D-glycero-α-D-galacto-heptopyranose derivative from 1,2:3,4-di-O-isopropylidene-α-D-galacto-hexodialdo-1,5-pyranose, methyl 2,3,4-tri-O-benzyl-D-hexodialdo-1,5-pyranosides with theglucoandmannoconfigurations showed no preference for the formation of compounds with theD-glyceroconfiguration. Attempts to achieve high diastereoselectivity in the conversion ofL-glycerointo theD-glyceroisomers by oxidation at C-6 followed by reduction withL-selectride were unsuccessful with the thiazole adducts, but the desired products were formed in similar reactions of methyl 2,3,4-tri-O-benzyl-7-O-tert-butyldimethylsilyl-D-heptopyranosides. The approach to homologation in thealtroseries was thwarted by epimerization at C-5 in the attempted formation of methyl 2,3,4-tri-O-benzyl-α-D-altro-hexodialdo-1,5-pyranoside. The successful synthesis of methylD-glycero-α-D-altro-heptopyranoside from methyl α-D-glucopyranoside was achieved by homologation followed by configurational alteration from theD-glucoto theD-altroseries.

ISSN:0008-4042    

DOI:10.1139/v94-036

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

Methyl α-D-glycopyranosides of 6-deoxy-D-altro-heptose, 6-deoxy-D-manno-heptose, and 6-deoxy-D-talo-heptose have been prepared. Displacements of methyl 2,3,4-tri-O-benzylhexopyranoside 6-trifluoromethanesulfonates with potassium cyanide, followed by reduction of the resulting heptopyranosidurononitriles with diisobutylaluminum hydride, hydrolysis of the imine, further reduction with sodium borohydride, and catalyticO-debenzylation, give the corresponding methyl 6-deoxyheptopyranosides. Configurational change at C-4 of methyl 6-deoxy-7-O-tert-butyldiphenylsilyl-α-D-manno-heptopyranoside to give thetaloisomer was effected by oxidation followed by stereoselective reduction.1H nuclear magnetic resonance data of the glycosides, and gas chromatography of acetylated glycosides of (R)- and (S)-2-butanol serve to establish ring and enantiomeric configurations of the parent sugars when these are encountered as constituents of lipopolysaccharides or extracellular carbohydrate polymers, as inCampylobacterspecies.

ISSN:0008-4042    

DOI:10.1139/v94-037

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

The conformations of the biologically active taxol analogs Taxotere®,3R,4R, and4S, and the biologically inactive analog3Swere evaluated in CDCl3and DMSO–water solution using1H NMR coupling constant and NOESY data and molecular modeling. The solution structures of Taxotere® were very similar to those detected previously for taxol. The A-ring side chain conformations of analogs3and4could not be defined with the same precision as had been possible for taxol, but the conformational possibilities could be significantly limited by the data. Analogs3R,4R, and4S(but not3S) can mimic the dominant conformation of taxol in chloroform, but no logical relationship between biological activity and aqueous solution conformation could be detected.

ISSN:0008-4042    

DOI:10.1139/v94-038

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

A protocol to separate the intermediates on the biosynthetic pathway to pantothenate on HPLC is described. Feeding experiments withL-[U-14C]valine to pea leaf disks result in incorporation of radioactivity into 2-ketoisovalerate, ketopantoyl lactone, and pantoyl lactone, providing the first experimental evidence that the biosynthetic pathway to pantothenate is the same in plants and bacteria.

ISSN:0008-4042    

DOI:10.1139/v94-039

出版商:NRC Research Press    

年代:1994

数据来源: NRC

摘要:

Allyldimethylsilyl triflate2may be prepared by a protiodesilylation reaction between diallyldimethylsilane and triflic acid. This compound possesses both a silyl-substituted carbon nucleophile and the Lewis acid necessary for activation of an electrophile. Upon exposure to an aromatic aldehyde (e.g.,p-MeOC6H4CHO), the homoallylic alcohol4is formed in good yield. The synthetic advantages of the intramolecular Cope-type cyclization reaction are discussed.

ISSN:0008-4042    

DOI:10.1139/v94-040

出版商:NRC Research Press    

年代:1994

数据来源: NRC