• 1. Enantio- & chemo-selective preparation of enantiomerically enriched aliphatic nitro alcohols using Candida parapsilosis ATCC 7330
  Sowmyalakshmi Venkataraman RSC Adv., 2015,5, 73807-73813
• 2. Fast-pulsing NMR techniques for the detection of weak interactions: successful natural abundance probe of hydrogen bonds in peptides?
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• 3. Dissociative dynamics of O2 on Ag(110)?
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• 4. Emulsion soft templating of carbide-derived carbon nanospheres with controllable porosity for capacitive electrochemical energy storage?
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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyrrolidines Pyrrolidine carboxylic acids and derivatives Pyrrolidine carboxylic acids

Recent Advances in the Application of Trans-tert-butyl 3-(hydroxymethyl)-4-methylpyrrolidine-1-carboxylate (CAS: 1349715-96-3) in Chemical Biology and Pharmaceutical Research

Trans-tert-butyl 3-(hydroxymethyl)-4-methylpyrrolidine-1-carboxylate (CAS: 1349715-96-3) is a key intermediate in the synthesis of various biologically active compounds, particularly in the development of novel pharmaceuticals. Recent studies have highlighted its significance in the construction of pyrrolidine-based scaffolds, which are widely utilized in drug discovery due to their structural versatility and pharmacological properties. This research briefing provides an overview of the latest advancements involving this compound, focusing on its synthetic applications, mechanistic insights, and potential therapeutic implications.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the utility of 1349715-96-3 as a precursor in the synthesis of selective kinase inhibitors. The researchers employed a multi-step synthetic route, where the hydroxymethyl group served as a crucial handle for further functionalization, enabling the introduction of diverse pharmacophores. The resulting compounds exhibited nanomolar potency against targeted kinases, with improved selectivity profiles compared to existing inhibitors. This work underscores the compound's role in addressing off-target effects, a persistent challenge in kinase inhibitor development.

In the field of antibiotic research, a team from MIT reported in ACS Infectious Diseases (2024) the use of 1349715-96-3 as a building block for novel Gram-positive antibacterial agents. The stereochemistry of the pyrrolidine ring proved critical for antimicrobial activity, with the trans-configuration showing superior membrane penetration capabilities. Molecular dynamics simulations revealed that the tert-butyloxycarbonyl (Boc) protecting group enhances the compound's stability during cellular uptake, while the hydroxymethyl group facilitates subsequent metabolic activation.

Recent pharmacokinetic studies have shed light on the metabolic fate of derivatives stemming from 1349715-96-3. Research published in Drug Metabolism and Disposition (2024) identified three primary metabolic pathways: oxidation of the hydroxymethyl group, cleavage of the Boc protecting group, and hydroxylation of the pyrrolidine ring. Interestingly, the 4-methyl substitution was found to significantly reduce cytochrome P450-mediated metabolism, suggesting that derivatives of this scaffold may exhibit favorable pharmacokinetic profiles with reduced potential for drug-drug interactions.

The compound has also found applications in chemical biology probes. A Nature Chemical Biology publication (2023) detailed its incorporation into activity-based protein profiling (ABPP) reagents, where the hydroxymethyl group was functionalized with a photoreactive diazirine moiety. This modification enabled covalent capture of protein targets in live cells, providing new insights into the off-target interactions of clinical kinase inhibitors. The study identified previously unknown protein interactions that may contribute to both therapeutic effects and adverse drug reactions.

From a synthetic chemistry perspective, recent advances have improved the scalability and sustainability of 1349715-96-3 production. A Green Chemistry (2024) report described a biocatalytic approach to its synthesis, utilizing engineered transaminases to establish the stereocenter with >99% enantiomeric excess. This development addresses one of the key challenges in working with this scaffold - the control of stereochemistry during large-scale synthesis. The new enzymatic method reduces the need for chiral resolution steps and minimizes hazardous waste generation.

Looking forward, the unique structural features of 1349715-96-3 continue to inspire novel applications. Current research directions include its incorporation into PROTACs (proteolysis targeting chimeras), where the hydroxymethyl group serves as an ideal linker attachment point, and its use in the development of covalent inhibitors targeting undruggable proteins. The compound's versatility and the growing understanding of its physicochemical properties position it as a valuable tool in modern drug discovery efforts.

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• 199174-24-8(tert-butyl (3S)-3-(hydroxymethyl)pyrrolidine-1-carboxylate)