Pd-catalyzed Arylation of 1,2-Amino Alcohol Derivatives via beta-Carbon Elimination

Herein, we describe a Pd-catalyzed arylation of 1,2-amino alcohols with aryl halides enabled by a retroallylation manifold. This protocol constitutes a new entry point to beta-arylated aldehydes via the intermediacy of in situ generated enamine intermediates. The protocol is characterized by its exquisite regioselectivity profile and broad substrate scope – including challenging substrate combinations –, even in an enantioselective manner

Chemoenzymatic One-Pot Process for the Synthesis of Tetrahydroisoquinolines

1,2,3,4-Tetrahydyroisoquinolines form a valuable scaffold for a variety of bioactive secondary metabolites and commercial pharmaceuticals. Due to the harsh or complex conditions of the conventional chemical synthesis of this molecular motif, alternative mild reaction pathways are in demand. Here we present an easy-to-operate chemoenzymatic one-pot process for the synthesis of tetrahydroisoquinolines starting from benzylic alcohols and an amino alcohol. We initially demonstrate the oxidation of 12 benzylic alcohols by a laccase/TEMPO system to the corresponding aldehydes, which are subsequently integrated in a phosphate salt mediated Pictet–Spengler reaction with m-tyramine. The reaction conditions of both individual reactions were analyzed separately, adapted to each other, and a straightforward one-pot process was developed. This enables the production of 12 1,2,3,4-tetrahydyroisoquinolines with yields of up to 87% with constant reaction conditions in phosphate buffer and common laboratory glass bottles without the supplementation of any additives.

Asymmetric Henry Reaction of Nitromethane with Substituted Aldehydes Catalyzed by Novel In Situ Generated Chiral Bis(β-Amino Alcohol-Cu(OAc)2·H2O Complex

Novel chiral thiophene-2,5-bis(β-amino alcohol) ligands (L1–L5) were designed and synthesized from thiophene-2,5-dicarbaldehyde (3) with chiral β-amino alcohols (4a–e) in 4 steps with overall 23% yields. An in situ generated L-Cu(OAc)2·H2O catalyst system was found to be highly capable catalyst for the asymmetric Henry reaction of nitromethane (7) with various substituted aromatic aldehydes (6a–m) producing chiral nitroaldols product (8a–m) with excellent enantiomeric purity (up to 94.6% ee) and up to >99% chemical yields. 20 mol% of L4-Cu(OAc)2 catalyst complex in EtOH was effective for the asymmetric Henry transformation in 24 h, at ambient temperature. Ease of ligand synthesis, use of green solvent, base free reaction, mild reaction conditions, high yields and excellent enantioselectivity are all key factors that make this catalytic system robust and highly desirable for the access of versatile building block β-nitro alcohol in practical catalytic usage via asymmetric Henry reaction.

Molecular Interaction Analysis of COX-2 Against Aryl Amino Alcohol Derivatives from Isoeugenol as Anti Breast Cancer using Molecular Docking

Breast cancer occurs due to uncontrolled cells proliferation. The Proliferation causes severe inflammatory which can be the initial stages of cancer symptoms. Aryl amino alcohol compounds from isoeugenol derivatives are proposed for the potential drugs of breast cancer. This study was conducted on iso-eugenol derivatives by adding carbonyl groups, hydroxyl groups, halide compounds and amines to determine the effect on anticancer activity through molecular docking studies. The molecular docking approach is carried out to see the interaction of ligands with protein compounds by using the minimized ligand energy bind with protein active site using protein data bank ID 5GMN. The docking result show that IE-Benzanilide-Cl (11) and IE-Benzanilide-OH (10) have the lowest binding energy (−8.3 kcal/mol and −8.6 kcal/mol) compare to another compounds. AdmetSAR computer simulations show that all compounds have very few toxic effects. The use of aryl amino alcohol derivatives (10 and 11) may be suggested as anti-breast cancer drugs. Copyright © 2021 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Pre-Clinical Activity of Amino-Alcohol Dimeric Naphthoquinones as Potential Therapeutics for Acute Myeloid Leukemia

Background: The clinical outcomes of patients with acute myeloid leukemia (AML) remain unsatisfactory, therefore the development of more efficacious and better-tolerated therapy for AML is critical. We have previously reported the anti-leukemic activity of synthetic halohydroxyl dimeric naphthoquinones (BiQ) and aziridinyl BiQ. Objective: This study aimed to improve the potency and bioavailability of BiQ compounds and investigate the anti-leukemic activity of the lead compound in vitro and in a human AML xenograft mouse model. Methods: We designed, synthesized, and performed structure-activity relationship of several rationally designed BiQ analogues that possess amino alcohol functional groups on the naphthoquinone core rings. The compounds were screened for anti-leukemic activity and the mechanism as well as in vivo tolerability and efficacy of our lead compound was investigated. Results: We report that a dimeric naphthoquinone (designated BaltBiQ) demonstrated potent nanomolar anti-leukemic activity in AML cell lines. BaltBiQ treatment resulted in the generation of reactive oxygen species, induction of DNA damage, and inhibition of indoleamine dioxygenase 1. Although BaltBiQ was tolerated well in vivo, it did not significantly improve survival as a single agent, but in combination with the specific Bcl-2 inhibitor, Venetoclax, tumor growth was significantly inhibited compared to untreated mice. Conclusion: We synthesized a novel amino alcohol dimeric naphthoquinone, investigated its main mechanisms of action, reported its in vitro anti-AML cytotoxic activity, and showed its in vivo promising activity combined with a clinically available Bcl-2 inhibitor in a patient-derived xenograft model of AML.