An iodobenzene-catalyzed oxidative rearrangement of 2-allylanilines was developed. This process involves an ortho-oxidative dearomatization mediated by the in situ generated iodine(III) compound and a subsequent aromatization-triggered rearrangement reaction, leading to the formation of functionalized indolin-3-ylmethanols with high diastereoselectivities.

A novel PhI(OAc)2-mediated dialkoxylation of 4-aminostyrenes has been developed. A range of 2,3-disubstituted 1,4-dioxane or 1,2-dimethoxyethane derivatives were formed in 15 to 95% yields with high diastereoselectivities. This transformation was distinct from the previously reported hypervalent iodine(III)-mediated dioxygenation reaction, a process via the formation of a cyclic iodonium ion intermediate. This protocol involves an oxidative dearomatization-induced nucleophilic attack and an aromatization-induced 1,6-conjugated addition.

A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine–quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28 ± 0.07 μM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.

A series of conformationally restricted dihydro-alkylthio-benzyl-oxopyrimidine (S-DABO) hybrids, which combined the structural features of C6-α-methylbenzyl-thio-DABOs (α-methyl-S-DABOs) and C6-α-cyanobenzyl-thio-DABOs (CN-S-DABOs), has been synthesized and biologically evaluated for their anti-HIV activity against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Most of these compounds exhibited inhibitory activity (wild-type) within the range of EC50 values from micromolar to nanomolar. Among them, compound 1s displayed the highest anti-HIV-1 activity with an EC50 value of 91 nM and a selectivity index (SI) of 548, which was more potent than zalcitabine and comparable to nevirapine and delavirdine in the same assay. The HIV-1 reverse transcriptase inhibitory (RT) assay confirmed that these conformationally restricted S-DABO hybrids targeted HIV-1 RT. The preliminary structure–activity relationship (SAR) and molecular docking analysis of this new series of conformationally constrained CN-S-DABO hybrids were also investigated.

An improved multikilogram-scale process for the production of (S)-1,2,4-butanetriol has been developed. This process involves the efficient removal of residual boric acid and the decomposition of the borate complexes formed during the reduction of (−)-dimethyl malate with sodium borohydride by methanolysis using a circular distillation-coupled hydrolysis apparatus.

A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26 μM and a selectivity index (SI) of 541. The preliminary structure–activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed.

A short and cyanide-free enantioselective synthesis of atorvastatin calcium has been achieved starting from a commercially available highly substituted 1,4-diketone in an overall yield of 40%. The key step in this approach is the asymmetric aldol reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)4–Schiff base complex to create the (5R)-stereochemistry of atorvastatin calcium.(R)-Isopropyl 7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-pheny1-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxoheptanoateC36H39FN2O5Ee = 82%[α]D20=+9.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration (R)(3R,5R)-Isopropyl 7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoateC36H41FN2O5Ee = 99%[α]D20=+14.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration (3R,5R)Isopropyl 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)ethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetateC39H45FN2O5[α]D20=+5.8 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration (4R,6R)Atorvastatin calciumC33H40CaFN2O8[α]D20=-7.5 (c 1.0, DMSO)Source of chirality: the precursorAbsolute configuration (3R,5R)

(+)-3a and (−)-3a were successfully separated from racemate (±)-3a by the chiral technique of supercritical fluid chromatography (SCF) with enantiomeric excess (ee%) >99% and purity >99%, and assigned for their absolute configuration as R and S, respectively, by the experimental electronic circular dichroism (ECD) spectrum and simulated ECD spectra calculated by time-dependent density functional theory (TDDFT) calculations. (+)-(R)-3a displayed excellent activity with an EC50 of 5.3 nM against wild-type HIV-1, which was 12-fold more potent than (−)-(S)-3a. However, (−)-(S)-3a showed higher potency than (+)-(R)-3a against the double HIV-1 RT mutant (K103N + Y181C) as well as HIV-2 strain ROD. The possible reason for the difference of (R)- and (S)-3a in anti-HIV-1 activity was interpreted by molecular docking.Graphical AbstractDiarylpyrimidines (+)-3a and (−)-3a were separated from racemate (±)-3a, assigned for their absolute configurations, and evaluated for their anti-HIV activity.Highlights► Diarylpyrimidines (+)- and (−)-3a were separated from (±)-3a. ► The absolute configurations of (+)- and (−)-3a were confirmed by ECD spectroscopy. ► (+)-(R)-3a and (−)-(S)-3a were evaluated for their anti-HIV activity.