Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification.

ABSTRACT: We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).

SUBMITTER: Gerard B

PROVIDER: S-EPMC3134123 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification.

Gerard Baudouin B Duvall Jeremy R JR Lowe Jason T JT Murillo Tiffanie T Wei Jingqiang J Akella Lakshmi B LB Marcaurelle Lisa A LA

ACS combinatorial science 20110428 4

We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The prod ...[more]

PMID: 21526820

Similar Datasets

Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol.

Project description:We have applied a diversity-oriented approach for the synthesis of skeletally diverse and stereochemically complex templates for small-molecule library production by performing Beckmann rearrangement and Beckmann fragmentation reactions on the bicyclo[3.2.1]octane rings of steviol and isosteviol, aglycones derived from the diterpene natural product stevioside. The optimization of these two reaction pathways is presented along with the successful application of a photo-Beckmann rearrangement. This work also led to the discovery of cyano-Prins-type and Thorpe-Ziegler-type cyclization reactions.

| S-EPMC3638842 | biostudies-literature

Library construction of stereochemically diverse isomers of spirooliganin: their total synthesis and antiviral activity.

Project description:The construction of libraries of stereoisomers of natural products serves as an important approach to investigating the correlation between the stereostructure and biological activity. However, the total synthesis and isomerzation of polycyclic scaffolds with multiple chrial centers are rare. Spirooliganin (1), a new skeleton natural product isolated from the plant Illicium oligandrum, was structurally characterized by comprehensive analysis of NMR spectroscopic data and ECD which revealed an unprecedented 5-6-6-6-7 polycyclic framework with six chiral centers. Here we report a 17-step total synthesis to prepare a library of stereochemically diverse isomers of spirooliganin, including 16 diastereoisomers and 16 regioisomers. In addition to a regioselective hetero-Diels-Alder cycloaddition, the synthetic strategy involves a photo-induced stereoselective Diels-Alder reaction, which gives only the abnormal trans-fused product as rationalized by density functional theory calculations. Preliminary biological evaluation showed that spirooliganin and regioisomers 39 exhibited potent inhibition of Coxsackievirus B3. It also revealed the pharmacophore effect of the D-ring (16R,18R,24R, and 26R) for their antiviral activities.

| S-EPMC8153216 | biostudies-literature

Accessing Stereochemically Rich Sultams via Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS) Scale-out.

Project description:The generation of stereochemically-rich benzothiaoxazepine-1,1'-dioxides for enrichment of high-throughput screening collections is reported. Utilizing a microwave-assisted, continuous flow organic synthesis platform (MACOS), scale-out of core benzothiaoxazepine-1,1'-dioxide scaffolds has been achieved on multi-gram scale using an epoxide opening/S(N)Ar cyclization protocol. Diversification of these sultam scaffolds was attained via a microwave-assisted intermolecular S(N)Ar reaction with a variety of amines. Overall, a facile, 2-step protocol generated a collection of benzothiaoxazepine-1,1'-dioxides possessing stereochemical complexity in rapid fashion, where all 8 stereoisomers were accessed from commercially available starting materials.

| S-EPMC3221740 | biostudies-literature

Rapid, scalable assembly of stereochemically rich, mono- and bicyclic acyl sultams.

Project description:A one-pot, sequential protocol is reported that involves complementary ambiphile pairing (CAP) of a vinyl sulfonamide with a variety of unprotected amino acids via aza-Michael addition and subsequent intramolecular amidation. The method generates diverse, sp(3)-rich mono- and bicyclic acyl sultams in a highly scalable manner. Modular pairing of stereochemically rich building blocks allows quick access to all possible isomers. Extension to include one-pot, sequential 3-, 4-, and 5-multicomponent protocols is also discussed.

| S-EPMC4179432 | biostudies-literature

Automated three-component synthesis of a library of ?-lactams.

Project description:A three-component method for the synthesis of ?-lactams from commercially available maleimides, aldehydes, and amines was adapted to parallel library synthesis. Improvements to the chemistry over previous efforts include the optimization of the method to a one-pot process, the management of by-products and excess reagents, the development of an automated parallel sequence, and the adaption of the method to permit the preparation of enantiomerically enriched products. These efforts culminated in the preparation of a library of 169 ?-lactams.

| S-EPMC3511015 | biostudies-literature

Access to Indole-Annulated Medium-Sized Lactams through Protonation/Deuteration-Induced Ring-Opening of Spiroindolines.

Project description:A protocol has been developed to access indole-annulated eight- and nine-membered lactams through protonation-induced ring-opening of spiroindolines, which are dearomative Heck products of tetrahydro-β-carbolines or hexahydroazepino[3,4-b]indoles. Brønsted acids and nucleophiles were explored and compared in the transformation. A combination of deuterated hydrochloride and deuterated methanol enables deuterative ring-opening of spiroindolines to afford medium-sized lactam diastereoisomers with a deuterium content ratio around 1:1.

| S-EPMC8482774 | biostudies-literature

Ugi Multicomponent Reaction Based Synthesis of Medium-Sized Rings.

Project description:An Ugi multicomponent reaction based two-step strategy was applied to generate medium-sized rings. In the first linear expansion phase, a series of diamines reacted with cyclic anhydrides to produce different lengths of terminal synthetic amino acids as the starting material for the second phase. The Ugi-4-center 3-component reaction was utilized to construct complex medium-sized rings (8-11) by the addition of isocyanides and oxo components. This method features mild conditions and a broad substrate scope.

| S-EPMC5698880 | biostudies-literature

Synthesis and screening of stereochemically diverse combinatorial libraries of peptide tertiary amides.

Project description:Large combinatorial libraries of N-substituted peptides would be an attractive source of protein ligands, because these compounds are known to be conformationally constrained, whereas standard peptides or peptoids are conformationally mobile. Here, we report an efficient submonomer solid-phase synthetic route to these compounds and demonstrate that it can be used to create high quality libraries. A model screening experiment and analysis of the hits indicates that the rigidity afforded by the stereocenters is critical for high affinity binding.

| S-EPMC3885906 | biostudies-literature

Synthesis of stereochemically and skeletally diverse fused ring systems from functionalized C-glycosides.

Project description:A diversity-oriented synthesis (DOS) strategy was developed for the synthesis of stereochemically diverse fused-ring systems containing a pyran moiety. Each scaffold contains an amine and methyl ester for further diversification via amine capping and amide coupling. Scaffold diversity was evaluated in comparison to previously prepared scaffolds by a shape-based principal moments of inertia (PMI) analysis.

| S-EPMC3752688 | biostudies-literature

Stereoselective synthesis of medium lactams enabled by metal-free hydroalkoxylation/stereospecific [1,3]-rearrangement.

Project description:Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex organic architectures. In contrast to the well-established [3,3]-rearrangement, [1,3] O-to-C rearrangement has been far less vigorously investigated, and stereospecific [1,3]-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations.

| S-EPMC6642132 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data