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Abstract: The key glycosyl donor for the target molecule 12 was prepared by two-step sequences; (1) acetalization of tert-butyldimethylsilyloxyacetaldehyde with 3-bromopropanediol, (2) DBN-initiated β-elimination of the resulting 2-(tert-butyldimethylsilyloxy)methyl-4-bromomethyl-1,3-dioxolane 11. Electrophilic glycosidation between 12 and silylated pyrimidine nucleobase proceeded efficiently to provide a mixture of β- and α-anomers of the respective glycosides 14 and 15. Tin radical-mediated reduction of the bromomethyl functional group of 14 and 15 gave protected 4′-C-methyl-dioxorane uracil- 16 and thymine nucleoside 17. The respective cytosine nucleoside 18 was synthesized from 16. De-silylation of 4′-methyl-1′,3′-dioxolane pyrimidine nucleosides 16–18 gave the target molecules. Evaluation of the anti-HIV-1 activity of the β- and α-anomers of the novel 4′-C-methyl-1′,3′-dioxolane nucleosides 22β,α–24β,α revealed that none of the nucleoside derivatives possess anti-viral activity against HIV-1 and show cytotoxicity against MT-4 cells at 100 μM. [Copyright &y& Elsevier]

Abstract: Synthesis of the 4′-ethynyl and 4′-cyano phosphonates 8–11, which mimic the 5′-monophosphate of 4′-branched 2′,3′-didehydro-2′,3′-dideoxy nucleosides, was investigated by employing the 3′,4′-unsaturated nucleosides (13 and 28) as the starting material. The synthesis was initiated by the electrophilic addition of NIS/(EtO)2P(O)CH2OH to these unsaturated nucleosides. After introduction of the 2′,3′-double bond, the 4′-hydroxylmethyl group of the resulting adducts was transformed into the ethynyl or cyano group. While the 4′-cyano phosphonates 9 and 11 were not sufficiently stable to be isolated, the 4′-ethynyl counterparts (8 and 10) were obtained as their mono-ammonium salts. The adenine derivative 8 showed almost comparable anti-HIV-1 activity to that of d4T. [ABSTRACT FROM AUTHOR]

Abstract: With an aim to synthesize 4′-substituted cordycepins, the 4′-benzoyloxy precursor (9) was prepared from adenosine through an electrophilic addition (iodo-benzoyloxylation) to the 4′,5′-unsaturated derivative (5) and subsequent radical-mediated removal of the 3′-iodine atom of the resulting adducts (6). Usefulness of 9 was briefly verified by synthesizing the 4′-allyl (12) and 4′-cyano (13) analogues of cordycepin. [Copyright &y& Elsevier]

Abstract: Desilylation of 1-[4-benzenesulfonyl-3-O-(tert-butyldimethylsilyl)-2-deoxy-5-O-methanesulfonyl-α-l-threo-pentofuranosyl]thymine (4) with Bu4NF/THF, when carried out at room temperature, gave four products. Among these, there were 1-[3-O-acetyl-4-benzenesulfonyl-2-deoxy-5-O-methanesulfonyl-α-l-threo-pentofuranosyl]thymine (7) and thymine. A possible reaction mechanism is proposed, which suggests the origin of 3′-O-acetyl group of 7 and thymine as well as structures of the other two products (9a and 9b). [Copyright &y& Elsevier]

Background: Bone distraction lengthening has been used for hand reconstruction. The healing process involved in this technique is affected by many factors. Here, the effectiveness and rates of healing of the phalanges and the metacarpals were evaluated in cases of traumatic finger amputation treated using an Ilizarov mini-fixator.Methods: Fourteen phalanges and twelve metacarpals in 15 patients (13 males and 2 females) were treated with distraction lengthening using an Ilizarov mini-fixator between 2014 and 2017. All the digits had been subjected to traumatic amputation, and shortening of the remaining digit had occurred despite successful replantation in some cases. The healing indices of phalanges and metacarpals were analyzed.Results: The mean patient age was 42.8 years. The mean lengthening of the phalanges was 13.3 mm, while that of the metacarpals was 26.5 mm. The mean consolidation times were 144.4 days for the phalanges and 154.1 days for the metacarpals. The mean healing indices of the phalanges and metacarpals were 114 days/cm and 60 days/cm, respectively. No bone grafts were needed in any of the patients.Conclusions: Distraction lengthening of the digits after traumatic amputation is an effective procedure for hand reconstructive surgery for either the phalanges or the metacarpals and is less invasive than other techniques. The rate of healing of the metacarpals is two times faster than that of the phalanges. [ABSTRACT FROM AUTHOR]

Objectives: According to epidemiologic surveys, the number of deaths from prostate cancer in Japanese men increased rapidly from 1970 to 2006. However, it is difficult to know the real incidence of, and mortality due to, prostate cancer because the reliability of death certificates and the cancer registry system in Japan are poor. Recently, several studies have demonstrated that baseline prostate-specific antigen (PSA) levels could be one of the most important predictive factors for developing prostate cancer. Therefore, we hypothesized that changes in the baseline PSA distribution in the screening population could reflect trends in the true incidence rate of prostate cancer. Methods: From 1988 to 2003, 32 274 men, aged 50-79 years, participated in population-based screening for prostate cancer for the first time in Gunma Prefecture, Japan. Changes in the baseline PSA distributions, stratified by a 5-year age range and calendar year, were investigated. The relationships between age and log10 PSA levels were also investigated and stratified by calendar year. Results: The median baseline PSA level was 0.9-1.2 ng/mL and had not recently increased. No specific trends were found in the percentages of participants with a PSA level greater than 2.0, 4.0, or 10.0 ng/mL within the same age range during the 16-year period. Conclusions: The increase in the incidence of, and mortality rates for, prostate cancer demonstrated by epidemiologic research might have been misleading in Japan. Investigational changes in the baseline prostate-specific antigen (PSA) distribution of the screened populations revealed that the true incidence rate of prostate cancer in Japan might have been almost the same during the past 16 years. [Copyright &y& Elsevier]