64298-90-4

Upstream product

• 81080-74-2 2-(2-cyanoethyl)alanine methyl ester 
• 124149-94-6 4-Cyano-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid methyl ester 
• 89775-75-7 3-methyl-2-oxopiperidine-3-carboxylic acid 

Downstream Products

• 59574-27-5 (R)-2-methylornithin 
• 48047-95-6 α-methyl-L-ornithine 
• 123979-17-9 N-(3-Methyl-2-oxo-piperidin-3-yl)-phthalamic acid 

Relevant academic research and scientific papers

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure - activity relationship (SAR) studies were also undertaken.

(S)-form of α-methyl-N(α)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-α production by human leukemia cell HL-60: implication of optical resolution of thalidomidal effects

The rate of racemization of N(α)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37°C. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-α production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-α-methyl-N(α)-phthalimidoglutarimides, (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-α production- enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.