Puwen Zhang

Regiospecific bromination of 3-methylindoles with N-bromosuccinimide

Abstract The regiospecific bromination of various substituted 3-methylindoles at either C(2) or the C(3) alkyl moiety was accomplished via an electrophilic or free radical bromination process to provide intermediates for indole alkaloid total synthesis. The regiospecificity of the bromination could be controlled by variation of both the substituent and the N(1) protecting group on the indole ring.

An enantiospecific synthesis of L(−)- and D(+)-6-Chloro-5-hydroxytryptophan: an unusual amino acid residue from the cyclic hexapeptide keramamide a

Abstract An enantiospecific synthesis of both L(−)- and D(+)-6-chloro-5-hydroxytryptophan 1a and important derivatives 1b and 1c was achieved in five steps from 6-chloro-5-methoxy-3-methylindole 2 .

A CONCISE SYNTHESIS OF OPTICALLY ACTIVE 2-BROMOTRYPTOPHAN AMINO ACIDS PRESENT IN KONBAMIDE AND JASPAMIDE VIA A REGIOSPECIFIC BROMINATION PROCEDURE

Abstract A highly stereoselective synthesis of optically active 2-bromo-5-hydroxy-tryptophan 1a and important derivatives 1b and 1c as well as their 2-bromotryptophan analogs was achieved in three steps from 2-bromo-3-bromomethylindoles 3a and 3b , respectively.

Syntheses of 5-thienyl and 5-furyl-substituted benzodiazepines: probes of the pharmacophore for benzodiazepine receptor agonists

Summary The synthesis of 5-thienyl and 5-furyl-substituted benzodiazepines is described. These compounds were employed to probe the lipophilic pocket ( L 3 ) of the benzodiazepine receptor (BzR) and to determine the effect of occupation of L 3 on biological activity. Of the new analogs synthesized, the 5-(2-thienyl)-benzodiazepines 6a and 7a displayed high affinity for the BzR (IC 50 28 and 18 nM, respectively) and exhibited both anticonvulsant (ED 50 ~ 9 and 3 mg/kg) and muscle relaxant (ED 50 ~ 10 and 7 mg /kg) activity. The 5-(3-thienyl)benzodiazepines 6d and 7d displayed only moderate affinity for the BzR (IC 50 140 and 110 nM) and exhibited no biological activity (no anticonvulsant or muscle relaxant activity) at doses up to 40 mg/kg. The 5-(2-furyl)benzodiazepines ( 6b, 7b, 19b and 20b ) exhibit low affinities for the BzR. These in vitro and in vivo findings are consistent with our model suggesting that pocket L 3 is very sensitive to lipophilic effects. Thus, decreasing the lipophilicity of functional groups which occupy this region decreases ligand affinity at BzR. The 2′-halogen (F or Cl) substituent of the 5-phenylbenzodiazepines increases ligand affinity in vitro because the active conformation of the phenyl N(4)=C(5)-C(1′)=C(2′) moiety is syn rather than anti . The syn conformation permits the 2′-halogen (F or Cl) atom to interact at the hydrogen bonding site H 2 and form a stable three-centered hydrogen bond in the proposed ligand binding cleft. The 3-thienyl and 2-furyl groups decrease the lipophilicity of the substituent which occupies L 3 but do not form a hydrogen bond at H 2 , thus resulting in a diminished affinity at BzR.

A successful acid promoted asymmetric pictet-spengler reaction of Na-BOC protected tryptophans. Effect of the BOC group on reactivity and stereoselectivity

Abstract N a -BOC protected tryptophans 1 and 2 successfully undergo the Pictet-Spengler cyclization with a series of aldehydes in the presence of an acid catalyst ( p -TSA) to furnish a mixture of trans and cis 1,2,3,4-tetrahydro-β-carbolines (3 and 4). During removal of the BOC function with TFA, the mixture of trans (3) and cis (4) isomers was enantiospecifically converted into the trans N a -H 1,2,3,4-teaahydro-β-carboline 5, a key intermediate for the construction of N a ,-H substituted sarpagine alkaloids.

Enantiospecific Synthesis of 5-Methoxy-D(+)- OR L(-) Tryptophan

Abstract A method for the enantiospecific synthesis of 5-methoxy-D(+)-tryptophan 8 or the L(-)-optical antipode is described. This procedure can be scaled up and performed without the need for extensive chromatographic separations. It provides for the first time the synthesis of the optically pure 5-methoxy-D(+) or L(-)-tryptophans required for alkaloid total synthesis.