[Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation].

Objective: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).

Methods: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.

Results: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis.

[Clinical and Bacteriological Analysis of Bacterial Bloodstream Infections in Patients with Acute Leukemial].

Objective: To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients.

Methods: Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed.

Results: A total of 376 strains were isolated, 76.

Synthesis of Chiral Piperazines via Hydrogenation of Pyrazines Activated by Alkyl Halides.

A facile method has been developed for the synthesis of chiral piperazines through Ir-catalyzed hydrogenation of pyrazines activated by alkyl halides, giving a wide range of chiral piperazines including 3-substituted as well as 2,3- and 3,5-disubstituted ones with up to 96% ee. The high enantioselectivity, easy scalability, and concise drug synthesis demonstrate the practical utility.

Design and synthesis of novel threosyl-5'- deoxyphosphonic acid purine analogues as potent anti-HIV agents.

The discovery of threosyl phosphonate nucleoside (PMDTA, EC₅₀ = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 5 '-deoxyversions of threosyl phosphonate nucleosides from 1,4-dihydroxy-2-butene. The synthesized nucleoside phosphonic acid analogues 14 and 19 were tested for anti-HIV activity as well as cytotoxicity.

Design and synthesis of novel 1',3'-dioxolane 5'-deoxyphosphonic acid purine analogues as potent antiviral agents.

Electronic parameters of 1',3 '-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1',3 '-dioxolane 5 '-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV.

Synthesis of novel 6'-spirocyclopropyl-5'-norcarbocyclic adenosine phosphonic Acid analogues as potent anti-hiv agents.

Novel 5'-norcarbocyclic adenosine phosphonic acid analogues with 6'-electropositive moiety such as spirocyclopropane were designed and synthesized from the commercially available diethylmalonate 5. Regioselective Mitsunobu reaction proceeded in the presence of an allylic functional group at a low reaction temperature in polar cosolvent [dimethylformamide (DMF)/1,4-dioxane] to give purine analogue 15. To improve cellular permeability and enhance the anti-human immunodeficiency virus (HIV) activity of this phosphonic acid, a SATE phosphonodiester nucleoside prodrug 23 was prepared.

Design and synthesis of dually branched 5'-norcarbocyclic adenosine phosphonodiester analogue as a new anti-HIV prodrug.

A novel 3',4'-dimethyl-5'-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line.

Design and synthesis of novel SATE derivatives of acyclic isocytosine and 9-deazaadenine C-nucleosides.

This article describes a very simple route for synthesizing novel lipophilic phosphate bis(t-bu-SATE) prodrugs of acyclic cyclobutylated C-nucleosides such as isocytosine 12 and 9-deazaadenine 19, which were prepared from 1,1-gem cyclobutyl dicarboxylate. Synthesized compounds were evaluated as potential antiviral agents against HIV virus. Some phosphate SATE prodrugs were more active against HIV than parent nucleosides.

Synthesis of 2'-fluoro and 2',4'-dimethyl pyrimidine C-nucleoside analogues as potential anti-HCV agents.

Stereoselective synthesis of novel 2'-fluoro and 2',4'-dimethyl carbocyclic pyrimidine C-nucleoside analogues using selective fluorination of an epoxide opening reaction is described. The key fluorinated intermediate 7 was prepared from the epoxide intermediate 5 via selective ring opening of the epoxide. Synthesis of isonucleosidic bases through the mesylate 7 and final deprotection provided the target carbocyclic pyrimidine C-nucleoside analogues.

Synthesis and anti-HIV activity of 4'-modified cyclopentenyl pyrimidine C-nucleosides.

Novel syntheses of 4'-modified cyclopentenyl pyrimidine C-nucleosides were performed via C-C bond formation using S(N)2 alkylation via the key intermediate mesylates 6 and 16, which were prepared from acyclic ketone derivatives. When antiviral evaluation of synthesized compound was performed against various viruses such as HIV-1, HSV-1 and HSV-2, isocytidine analogue 20 showed moderate anti-HIV activity in CEM cell line (EC(50) = 13.1 micromol).

Synthesis and anti-hepatitis C virus activity of 2'(beta)-hydroxyethyl and 4'(alpha)-hydroxymethyl carbodine analogues.

2'(beta)-Hydroxyethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication targeting the RNA-dependent RNA polymerase of HCV, NS5B. The synthesis and anti-HCV evaluation of carbodine analogues are described. The cyclopentene intermediate 10 was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis.

Short synthesis and antiviral activity of acyclic phosphonic acid nucleoside analogues.

An efficient route for synthesizing novel allylic and cyclopropanoid phosphonic acid nucleoside analogues is described. The condensation of the bromine derivatives 6 and 18 with nucleoside bases (A, U, T, C, G) under standard nucleophilic substitution and deprotection conditions, afforded the target phosphonic acid nucleoside analogues. These compounds were evaluated for their antiviral properties against various viruses.

Efficient synthesis of 4'-cyclopropylated carbovir analogues with use of ring-closing metathesis from glycolate.

The first synthetic route of novel 4'-cyclopropylated carbovir analgues is described. The construction of cyclopropylated quaternary carbon at 4'-position of carbocyclic nucleosides was successfully made via sequential Johnson's orthoester rearrangement and ring-closing metathesis (RCM) starting from ethyl glycolate. Synthesized compounds 15 and 16 showed moderate antiviral activity without any cytotoxicity up to 100 micromol.

First synthesis and anti-HIV evaluation of 4'-methyl-cyclopentanyl 9-deazaadenosine.

The first synthesis of a 4'-methylated carbocyclic C-nucleoside 16 was achieved via the mesylate intermediate 10, which was prepared using ring-closing metathesis and S(N)2 alkylation from acetol 5. When antiviral evaluation of synthesized compound 16 was performed against various viruses such as HIV, HSV-1, HSV-2, and HCMV, it showed moderate anti-HIV activity in MT-4 cell line (EC(50) = 14.7 micromol).