Enantioselective Synthesis of Cyclothiazide Analogues:  Novel Probes of the Stereospecific Actions of Benzothiadiazines at AMPA-Type Glutamate Receptors

Abstract

The stereospecific interactions of the eight stereoisomers of dihydromethylcyclothiazide, an analogue of cyclothiazide, with AMPA-type glutamate receptors was investigated using electrophysiological methods that measured the ability of each stereoisomer to inhibit AMPA receptor desensitization. The eight stereoisomers were obtained by HPLC separation of four pairs of enantiomerically pure (>95% ee) diastereomers prepared from (1R-exo)-, (1R-endo)-, (1S-exo)-, and (1S-endo)-2-methylbicyclo[2.2.1]heptane-2-carboxaldehyde intermediates. The desensitization process was blocked most potently by [1S-[1R,2R(R*),4R]]-dihydromethylcyclothiazide, one of the stereoisomers prepared from the (1S-endo)-carboxaldehyde. The smallest effects on the desensitization process were found for the four stereoisomers prepared from the (1R-exo)-and (1R-endo)-carboxaldehydes. Significant differences in the ability to inhibit desensitization were observed between all diastereomer pairs except those prepared from the (1S-exo)-carboxaldehyde.

An improved synthesis of aziridine-2,3-dicarboxylates via azido alcohols—epimerization studies

“…The tartrates (R,R)-1c and (S,S)-1c were prepared according to literature, with their analytical data corresponding to literature values. 43 …”

Cationic Gemini Surfactants Based on Tartaric Acid: Synthesis, Aggregation, Monolayer Behaviour, and Interaction with DNA

“…[20] Subsequent introduction of the alkyl chains and catalytic removal of the benzyl groups afforded the key compound 3 in an overall yield of 85% (Scheme 1). The preparations of the protected head groups 6 and 8 started from commercially available N α -Boc-N ε -Z--lysine (4, Scheme 1).…”

“…[20] Dibenzyl (2R,3R)-2,3-Bis(hexadecanoyloxy)butanedioate (2): A solution of 1 (1.01 g, 3.1 mmol) in CHCl 3 (20 mL) with triethylamine (1 mL, 7.2 mmol) and a catalytic amount of DMAP was gradually added to a cooled (0°C) solution of hexadecanoyl chloride (1.71 g, 6.2 mmol) in CHCl 3 (10 mL). The reaction mixture was allowed to warm to room temperature and then stirred for a further 1 h. The reaction mixture was diluted with CHCl 3 and washed with 1.5  HCl, 10% (w/v) NaHCO 3 solution, brine, dried (MgSO 4 ), and concentrated in vacuo.…”

Tartaric acid and its acyl derivatives. Part 5. Direct synthesis of monoacyltartaric acids and novel mono(benzoyl)tartaric anhydride: unusual findings in tartaric acid acylation

“…The most frequently used procedure to obtain acids 2 requires multi-step reactions (Scheme 1): the protection of the tartaric acid 1 carboxylic groups (usually by the benzyl esters using method a or b), an appropriate acylation (method c or d or e), and deprotection as the last step (method f). 18,22,[24][25][26][27][28][29][30] However, the monoacylation of diester 5 itself remains challenging. It requires the addition of an amine and a catalyst when using an acid chloride (method c), or coupling agents (DCC or TFAA) in the acylation with an appropriate carboxylic acid (method d or e).…”

“…It requires the addition of an amine and a catalyst when using an acid chloride (method c), or coupling agents (DCC or TFAA) in the acylation with an appropriate carboxylic acid (method d or e). e: RCOOH/TFAA, [29][30][31] f: H 2 /Pd/C.…”