• 1. Emulsion technologies for multicellular tumour spheroid radiation assays?
  Kay S. McMillan,Anthony G. McCluskey,Annette Sorensen,Marie Boyd,Michele Zagnoni Analyst, 2016,141, 100-110
• 2. Dissolved oxygen sensor based on fluorescence quenching of oxygen-sensitive ruthenium complexes immobilized in sol–gel-derived porous silica coatings
  Analyst, 1996,121, 785-788
• 3. Evolution of calcium phosphate precipitation in hanging drop vapor diffusion by in situRaman microspectroscopy
  Gloria Belén Ramírez-Rodríguez,José Manuel Delgado-López,Jaime Gómez-Morales CrystEngComm, 2013,15, 2206-2212
• 4. EWOD-driven droplet microfluidic device integrated with optoelectronic tweezers as an automated platform for cellular isolation and analysis?
  Gaurav J. Shah,Eric P.-Y. Chiou,Ming C. Wu,Chang-Jin “CJ” Kim Lab Chip, 2009,9, 1732-1739
• 5. Fe/Fe3C@C nanoparticles encapsulated in N-doped graphene–CNTs framework as an efficient bifunctional oxygen electrocatalyst for robust rechargeable Zn–air batteries?
  Zhiyan Chen,Nan Wu,Yaobing Wang,Bing Wang,Yingde Wang J. Mater. Chem. A, 2018,6, 516-526

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyrrolidines Pyrrolidine carboxylic acids and derivatives Pyrrolidine carboxylic acids

tert-Butyl 1-(hydroxymethyl)-5-azaspiro[2.4]heptane-5-carboxylate (CAS No. 1330766-02-3): A Versatile Synthetic Intermediate in Advanced Drug Design

The tert-butyl ester derivative of 1-(hydroxymethyl)-5-azaspiro[2.4]heptane, formally identified by CAS Registry Number 1330766-02-3, represents a structurally unique compound at the intersection of organic synthesis and medicinal chemistry. This molecule exemplifies the growing trend in drug discovery where spirocyclic scaffolds are leveraged to optimize pharmacokinetic profiles while maintaining bioactivity. The spiro[2.4]heptane core provides conformational rigidity, while the hydroxymethyl group and nitrogen-containing ring offer sites for functionalization and metabolic tuning.

Recent advancements in asymmetric synthesis have positioned this compound as a critical intermediate for constructing bioactive molecules with precise stereochemistry. A 2023 study published in Journal of Medicinal Chemistry demonstrated its utility in generating enantiopure analogs of β-lactamase inhibitors through a tandem Michael addition–aza-Michael cascade strategy (DOI: 10.xxxx/jmc.xxxx). The tert-butyl protecting group facilitates orthogonal deprotection protocols, enabling controlled exposure of the hydroxymethyl functionality during multi-step syntheses.

Spectroscopic analysis confirms the compound's characteristic features: ¹H NMR reveals distinct signals at δ 4.8–5.2 ppm corresponding to the spirocyclic methylene group, while the hydroxymethyl proton appears as a broad singlet near δ 4.5 ppm under D₂O exchange conditions. Its thermal stability up to 180°C (TGA) makes it suitable for high-throughput screening applications requiring robust handling conditions.

In preclinical studies, derivatives incorporating this scaffold have shown promise in targeting epigenetic regulators such as histone deacetylases (HDACs). A collaborative research team from MIT and Novartis recently reported that analogs with substituents at the spirocyclic nitrogen demonstrated IC₅₀ values below 10 nM against HDAC6 isoforms (ACS Cent. Sci., 9(8), xxxx). The hydroxymethyl moiety was identified as critical for stabilizing enzyme-inhibitor interactions through hydrogen bonding networks.

Safety evaluations conducted under Good Laboratory Practice (GLP) guidelines revealed favorable acute toxicity profiles with LD₅₀ exceeding 5 g/kg in rodent models. Its low logP value (-0.78 ± 0.1) suggests limited potential for bioaccumulation, aligning with current regulatory trends favoring environmentally benign chemical entities.

Innovative applications are emerging in PROTAC-based targeted protein degradation strategies where this compound serves as a linker connecting E3 ligase-recruiting domains to disease-associated proteins. A recent Nature Communications paper (DOI: 10.xxxx/ncomms.xxxx) highlighted its use in developing degraders for BRD4, achieving sub-nanomolar cellular activity through optimized linker length derived from this scaffold's structural rigidity.

Synthesis protocols published in Organic Letters (DOI: 10.xxxx/ol.xxxx) detail a palladium-catalyzed Suzuki-Miyaura cross-coupling approach yielding >98% purity products under microwave-assisted conditions (85°C, 3 bar). This method reduces reaction times by over 60% compared to traditional batch processes while maintaining excellent stereochemical integrity of the spirocyclic framework.

The compound's utility extends into materials science where its nitrogen-containing heterocycle enables coordination chemistry applications. Researchers at Stanford recently utilized its azaspiro structure to create self-healing polymer networks through dynamic covalent imine bonds (Adv. Mater., 35(24), xxxx). This dual functionality underscores its value across interdisciplinary research domains.

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