VRC-4334

Chemical Name: 3(R)-Amino-5(R)-hydroxy-6-(methylamino)hexanoic acid 2-(carboxymethyl)-2-methylhydrazide ; 2-[2-[3(R)-Amino-5(R)-hydroxy-6-(methylamino)hexanoyl]-1-methylhydrazino]acetic acid
项目整合开发状态: Preclinical
项目研究机构: Vicuron Pharmaceuticals (Originator)
合成路线:The reaction of 3(R)-(tert-butoxycarbonylamino)-5-hexenoic acid (I) first with KI and I2,and then with NaN3 gives 6-azido-3(R)-(tert-butoxycarbonylamino)hexano-5-lactone (II),which is hydrolyzed with LiOH and protected with Tbdms-Cl to yield 6-azido-3(R)-(tert-butoxycarbonylamino)-5-(tert-butyldimethylsilyloxy)hexanoic acid (III).The reaction of acid (III) with pentafluorophenyl trifluoroacetate affords the corresponding activated ester as a mixture of diastereomers (IV) + (V).After separation,the desired diastereomer (IV) is condensed with 2-(1-methylhydrazino)acetic acid tert-butyl ester (VI) to provide the corresponding hydrazide (VII),which is reduced at the azido group by means of PPh3 in THF/water to give the amino compound (VIII).The condensation of (VIII) with 2-nitrophenylsulfonyl chloride (IX) by means of collidine in dichloromethane yields the sulfonamide (X),which is methylated with MeI and Cs2CO3 in DMF to afford the N-methylsulfonamide (XI).Finally,this compound is deprotected by reaction first with PhSH and K2CO3 and then with 4M HCl to provide the target hydrazide.