Simultaneous regioselective protection of phenyl 1-thioglucosides at the C-3 and C-6 or at the C-2 and C-6 hydroxy groups

Simultaneous regioselective 3,6- or 2,6-selective protection of 1-thio-beta- or alpha-D-glucopyranosides is described. The C-3 and C-6 hydroxy groups of the beta-thioglucoside were selectively protected with triisopropylsilyl or tert-butyldiphenylsilyl trifluoromethanesulfonate. The C-2 and C-6 hydroxy groups of the alpha-thioglucoside were selectively protected with tert-butyldiphenylsilyl trifluoromethanesulfonate.     

Confirmation of the Relative Stereochemistry at C-23 and C-24 of Tautomycin

Degradation product including the moiety for C-19 through to C-25 of tautomycin were synthesized. This synthesis confirmed the relative stereochemistry at C-23 and C-24 of tautomycin.     

Synthesis and biological evaluation of C-3'NH/C-10 and C-2/C-10 modified paclitaxel analogues

Concurrent modifications on the C-3'NH/C-10, and C-2/C-10 positions on paclitaxel were carried out as a way of investigating possible synergistic effects. The biological activities of these analogues were evaluated in both a microtubule assembly assay and human ovarian cancer (A2780) and prostate cancer (PC3) cytotoxicity assay. In some cases the doubly modified analogues were more active than would have been predicted based on the activity of the singly modified analogues, indicating probable synergistic effects.     

On the side-chain conformation of N-acetylneuraminic acid and its epimers at C-7, C-8, and C-7,8

The side-chain conformation of N-acetylneuraminic acid and analogs has been studied by n.m.r. spectroscopy. The results of the 1H-, 13C-n.m.r.-, and 1H-nuclear-Overhauser-enhancement measurements were used to distinguish between different local-minima conformations suggested by hard-sphere calculations. Attempts were made to correlate the major conformation determined for each compound with the behavior towards activation with N-acetylneuraminic acid-CMP-synthetase.     

Investigation of the specificity of an alpha-L-arabinofuranosidase using C-2 and C-5 modified alpha-L-arabinofuranosides

The synthesis of three novel glycosyl donors presenting the same scaffold as alpha-L-arabinofuranose but modified at the C-2 or C-5 positions has been achieved. Furthermore, chemoenzymatic syntheses using the alpha-L-arabinofuranosidase AbfD3 and these unnatural furanosides were investigated. The use of the novel p-nitrophenyl furanoside donors revealed that AbfD3 can perform transglycosylation with the C-5 deoxygenated donor but not with the C-2 modified one. These results emphasize the vital role for OH-2 in AbfD3 substrate recognition.     

Metabolism of 17 alpha-methyltestosterone in the rabbit: C-6 and C-16 hydroxylated metabolites

17 alpha-Methyltestosterone and the reduced metabolites, 17 alpha-methyl-5 alpha-androstane-3 alpha, 17 beta-diol, 17 alpha-methyl-5 alpha-androstane-3 beta, 17 beta-diol and 17 alpha-methyl-5 beta-androstane-3 alpha, 17 beta-diol, together with three hydroxylated metabolites, 17 alpha-methyl-5 beta-androstane-3 alpha, 16 alpha, 17 beta-triol, 17 alpha-methyl-5 beta-androstane-3 alpha, 16 beta, 17 beta-triol and a new metabolite, 17 alpha-methyl-5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol, were isolated and identified in the urine of rabbits dosed with 17 alpha-methyltestosterone. No hydroxylated 5 alpha-metabolite of 17 alpha-methyltestosterone has been identified previously. No of 17 alpha-methyltestosterone has been identified previously. No evidence for epimerization at the C-17 position was observed.     

Stereochemistry of the biogeneration of C-10 and C-12 gamma lactones inYarrowia lipolytica andPichia ohmeri

Summary Degradation of the C-16 and C-18 racemic hydroxy acids 1–4 to C-10 and C-12 -lactones 5–8 proceeds inYarrowia lipolytica andPichia ohmeri with opposite stereochemistry     

Synthesis of C-2 and C-4 deuterium-labeled estradiol-17 beta

Estradiol-17 beta labeled with deuterium in the positions 2 or 4 can be prepared from 2-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol 3-methyl ether 17-acetate or 4-chloromercurio-1,3,5(10)-estratriene-3,17 beta-diol, respectively, in refluxing CH3COO(2)H/(2)H2O. The same reaction performed on 4-acetoxymercurio-1,3,5(10)-estratriene-3,17 beta-diol afforded 2,4-dideuterio-estradiol-17 beta in good yields.     

磷脂酶C—γ2对鼠成纤维细胞株迁移能力的影响

通过对敲除磷脂酶C－γ1基因的鼠成纤维细胞株及其转染磷脂酶C-γ2的迁移指标的统计学分析,揭示出磷脂酶C－γ1和γ2在PDGF引起的细胞迁移信号传导中均有正调控作用,前者作用显著而后者作用微小,并且仅在磷脂酶C-γ1功能缺失的条件下方可发挥出来,同时进一步证明敲除磷脂酶C－γ1基因的细胞株中,未见出现磷脂酶C－γ2的代偿,说明磷脂酶C－γ2与在功能上不可相互取代,反映了一种信号可由多种途径传导即细胞信号传导的交互性,沉余性。     

Steric effects at C-20 and C-24 on the metabolism of sterols by Tetrahymena pyriformis

Cultures of Tetrahymena pyriformis were incubated with various sterols and the extent of dehydrogenation at C-7 and C-22 was determined. The sterols incubated were desmosterol, 22-dehydrodesmosterol, 24-methyldesmosterol, 24 alpha-methylcholesterol (campesterol), 24-methylene-cholesterol, isohalosterol (26,27-bisnorcampesterol, also known as 24,24-dimethylchol-5-en-e beta-ol, a naturally occurring C26-sterol), and 20-isohalosterol. 20-Isohalosterol was not metabolized, while products with delta 7- and delta 22-bonds were formed from isohalosterol and all of the other sterols studied. This confirms an earlier conclusion, based on results with 20-isocholesterol and cholesterol, that inversion of the configuration from 20(R) to 20(S) completely prevents metabolism both in the nucleus and the side chain. On the other hand, changes in the electronics or stereochemistry at C-24 had a direct affect only on metabolism in the side chain. The presence of a methyl group at C-24 reduced the yield of metabolites with a delta 22-bond relative to those with a delta 7-bond producing an accumulation of 7-dehydro metabolite. A double bond at position-24 counteracted this steric effect, presumably by enhancing the rate of dehydrogenation, and a delta 24(28)-bond was more effect than was a delta 24(25)-bond.     

磷脂酶C-γ2在鼠成纤维细胞株克隆形成中的作用

通过对敲除磷脂酶C-γ1基因的细胞株及其转染磷脂酶C-γ2基因后克隆形成能力的统计学分析揭示出磷脂酶C-γ2有显著的促克隆形成作用,磷脂酶C-γ1作用微小,但与磷脂酶C-γ2有协同作用,提示磷脂酶C-γ2与γ1在功能上有一定的交互性、冗余性,但不可相互取代.     

Synthesis and Biological Activity of Some Juvenile Hormone Analogs Lacking the Alkyl Substituents at C-7 or Both at C-3 and at C-7

Two groups of juvenile hormone analogs were synthesized. One lacks the alkyl substituent at C?7. The other possesses the alkyl substituents neither at C?3 nor at C?7. These analogs were almost inactive on Bombyx mori L. Some of them with the alkyl substituent at C?3, however, were active on Tenebrio molitor L. This indicates the very narrow sensitivity of Bombyx mori L. to juvenile hormone analogs.     

Modifications at C-3 and C-4 of 2-amino-2-deoxy-d-glucose

Modifications at C-3 and C-4 of 2-amino-2-deoxy-d-glucose have been developed. A 3,4-double bond was introduced into benzyl 2-acetamido-2-deoxy-3,4-di-O-Methylsulfonyl-α-d-glucopyranoside by treatment with NaI and Zn. Epoxidation of the double bond with m-chloroperoxybenzoic acid gave an exo-epoxide exclusively. The stereochemistry of the epoxidation product has been confirmed by an alternative synthesis. An analysis of the ¹H-n.m.r. spectra indicates that both the 3,4-unsaturated derivatives and the epoxide exist in the °H₁ (d) conformation. Nucleophilic reagents (F^?, I^?) opened the 3,4-epoxide to give 4-substituted derivatives having the d-gulo configuration. Thus, 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-iodo-α-d-gulopyranose and 2-acetamido-1,3,6-tri-O-acetyl-3,4-dideoxy-4-fluoro-α-d-gulopyranose have been synthesized. Reduction of the double bond in the key intermediate and deprotection gave 2-acetamido-2,3,4-trideoxy-d-glucopyranose. Some of the derivatives were active as inhibitors of growth of mouse, mammary adenocarcinoma cells in culture.     

Comparative studies of NADP-malic enzyme from C-4 and C-3 plants

Some enzymological properties were studied comparatively for NADP-malic enzyme from various C₄- and C₃-plants. The enzyme from C₄-plants of “malate formers” showed relatively low Km(Mal) values (0.10 – 0.25 mM) and high pH optima (more than pH 7.4 – 7.8). Contractively, the enzyme from the other groups of higher plants including C₄-plants of “aspartate formers”, C₃-plants and CAM-plant showed relatively high Km(Mal) values (0.68 – 1.05 mM) and low pH optima (less than pH 7.4).     

Association of RrgA and RrgC into the Streptococcus pneumoniae pilus by sortases C-2 and C-3

Pili are surface-exposed virulence factors involved in the adhesion of bacteria to host cells. The human pathogen Streptococcus pneumoniae expresses a pilus composed of three structural proteins, RrgA, RrgB, and RrgC, and requires the action of three transpeptidase enzymes, sortases SrtC-1, SrtC-2, and SrtC-3, to covalently associate the Rrg pilins. Using a recombinant protein expression platform, we have previously shown the requirement of SrtC-1 in RrgB fiber formation and the association of RrgB with RrgC. To gain insights into the substrate specificities of the two other sortases, which remain controversial, we have exploited the same robust strategy by testing various combinations of pilins and sortases coexpressed in Escherichia coli. We demonstrate that SrtC-2 catalyzes the formation of both RrgA-RrgB and RrgB-RrgC complexes. The deletion and swapping of the RrgA-YPRTG and RrgB-IPQTG sorting motifs indicate that SrtC-2 preferentially recognizes RrgA and attaches it to the pilin motif lysine 183 of RrgB. Finally, SrtC-2 is also able to catalyze the multimerization of RrgA through the C-terminal D4 domains. Similar experiments have been performed with SrtC-3, which catalyzes the formation of RrgB-RrgC and RrgB-RrgA complexes. Altogether, these results provide evidence of the molecular mechanisms of association of RrgA and RrgC with the RrgB fiber shaft by SrtC-2 and SrtC-3 and lead to a revised model of the pneumococcal pilus architecture accounting for the respective contribution of each sortase.     

Structure-activity relationships of estrogens. Effects of 14-dehydrogenation and axial methyl groups at C-7, C-9 and C-11

Thirty compounds were evaluated in the rat for uterotropic effects, inhibition of gonadotropin release, and competitive displacement of (3H) estradiol-17 beta from uterine cytosolic preparations. 7 alpha-Methylestradiol-17 beta was 150% as active as estradiol-17 beta as an uterotropic agent. Estradiol-17 beta was the most active inhibitor of gonadotropin release. 11 beta-Methylestradiol-17 beta had 124% of the activity of estradiol-17 beta in displacing (3H) estradiol-17 beta from the "estrogen receptor." The 9 alpha-methyl group considerably decreased the potency of estrogens in any of the three assays. The 14-dehydro modification was advantageous only in the estradiol-17 beta 3-methyl ether series. Uterotropic activities and inhibition of gonadotropin release did not parallel. The best compound for inhibiting gonadotropin release, as compared to uterotropic activity, was estrone. The "estrogen receptor" assay data correlated fairly well with uterotropic assay data, but only for compounds having free 3-hydroxyl groups; even so, some exceptions were noted.