melphalan

Place syntheses below.

~Amanda Stampas~ Your protection step is probably workable, except that the usual way to deprotect a phthalimide is with hadrazine. This would react with the chloride. Possibly strong acid would work though. the synthesys of phenylalenine would not work at all because you can not put a cation on the alpha carbon. It is nucleophilic, not electrophilic. You would do best synthesizing the phenylalanine by way of the strecker synthesis. It is a mannich reaction involving an aldehyde, amonium ion, and cyanide ion.

MELPHALAN, IS PREPAERED BY A STARTING REAGENT OF PHENYL ALAMINE. THE PHENYL ALAMINE IS A READILY AVAILABLE MATERIAL OF FGA. THE FIRST PHENYL ALAMINE IS NITRATED WITH NITRATING ACID MIXTURE. SINCE, THE ORTHO POSITION IS STERICALLY HINDERED, THEN THE NITATING ALMOST EXCLUSIVELY TAKE PLACE AT A PARA POSITION. THEN SUBSEQUENTLY, THE P-NITRO DERIVATIVE IS REDUCED TO AMINE. BY METHOD OF MATERIAL ACID REDUCTION SYSTEM (Sn/HCL). THE PRIMARY AMINE STILL PRODUCE IS N-ALKYLATED WITH 2 EQ. OF DICHLOROETHANE TO FORM MALPHALAN. GIVES THE SELECTIVE PRODUCT FORMATION. REF, PRINCIPLE OF ORGANIC SYNTHESIS. 3RD ED. BY S.K GHOSH. NEW CENTRO PUB. INDIA. WADE. ORGO BOOK. //**( CHARLES IGWE, JOSEPH WILLIAMS. DIONNE MILAN).**// Charles, Josepht and Dionne: This is a nice straight forward synthesis. Does the amino group of the amino acid part have to be protected during the nitration and alkylation steps? It could react preferentialy durning the alkylation, because it is more basic, and therefor more nucleophilic than the aromatic amine. Bruce Bondurant

Dr B, You asked a question whether Amino group of the Amino acid part need to be protected during the nitration and alkilation step.

The answer is yes. It is a general procedure to protect the Amino group of the Amino acid during the Amino acid base synthesis reaction,because it could react preferably during the alkylation, it is more basic and therefore more nucleophilic than the aromatic amine.
 * //CHARLES IGWE, JOSEPH WILLIAMS. DIONNE MILAN//**


 * //Thank you very much Dr B for all your help and may God bless you.//**