12-07-03 16:56
No 475296
I have been searching all day, I am trying to find synthesis of alpha-methyl-phenylalanine. Rhodium suggested the use of benzaldehyde and provided the link a while back, although the link is now broken...
J. Med. Chem. 14(11), 1132-1133 (1971)
pharmacist.the-hive.tripod.com/alal-amph
Rhodium also said there was a way from phenylalanine that involved PTC(phase transfer) but that proved untested and hard to find in the search engines at the sites upon sites.
I did however find an article describing the use of a-methylphenylalanine as a diet supplement, it showed a study in rats, I can provide a link if interested (the link isn't too compelling)
Can someone post the article from the J. Med. Chem.? I have been searching all day, the good side is I can now type phenylalanine as a reflex.
--Word on the street is, You Reap What You Sow
(Moderator)
12-07-03 18:18
No 475307
Here it is:
J. Med. Chem. 14(11), 1132-1133 (1971)
Chemistry is our Covalent Bond
(Hive Bee)
12-09-03 13:32
No 475706
A practical asymmetric synthesis of a-methyl a-amino acids using a chiral Cu–salen complex as a PTC
DOI:10.1016/S0040-4039(00)01247-8
Abstract
The asymmetric C-alkylation of N-benzylidene alanine methyl ester has been achieved using a copper(II) (salen) complex as an asymmetric phase transfer catalyst and provides a practical synthesis of a-methyl a-amino acids with up to 86% enantiomeric excess.
Tetrahedron Letters
Volume 41, Issue 37 , September 2000, Pages 7245-7248
Other PTC Reactions
DOI:10.1016/S0957-4166(99)00185-8
Abstrct
Enantiopure 2-hydroxy-2'-amino-1,1'-binaphthyl (NOBIN) is shown to catalyse C-alkylation of aldimine Schiff's bases of alanine ester under phase-transfer catalysis conditions (solid NaOH or NaH, toluene, ambient temperature, 10% NOBIN). Using (R)-NOBIN, the final (S)-a-methylphenylalanine was obtained in up to 68% ee.
DOI:10.1016/S0957-4166(98)00044-5
Abstrct
Compound (4R,5R)- or (4S,5S)-2,2-dimethyl-a,a,a',a'-tetraphen
DOI:10.1016/S0040-4039(99)01836-5
Abstract
Application of N-anthracenylmethyl dihydrocinchonidinium bromide as a catalyst for the enantioselective alkylation of a series of alanine-derived imines is reported. Using solid K2CO3/KOH as the stochiometric base such alkylations can be achieved with enantiomeric excesses up to 87% allowing rapid access to a,a-dialkyl-a-amino acid esters.
I am mainly interested in the Copper salen reaction, but the other PTC's wouldn't bother me if they weren't so exotic. Can someone explain to me chiral Cu-Salen complexes? There was another interesting one that I couldn't access the abstract to, titled........ "Asymmetric PTC C-Alkylation Catalyzed by Chiral Derivatives of Tartaric Acid and Aminophenols" found on Beilstein, J.Org.Chem. , Jan 2000.
--Word on the street is, You Reap What You Sow
(Hive Bee)
12-10-03 00:20
No 475893
Anybee who has seen the article or who might be able to speculate - would formaldehyde be a suitable candidate to form the imine (aldimine) - its the obvious choice since this would lead to the desirable n-methyl structure following decarboxylation),
fucking great refs... - very interesting, well done LucidD.
(Hive Bee)
12-11-03 16:15
No 476255
Well, apparently, the alkylation can also be acheived by treating the ester with a methyl halide; methyl chloride, methyl iodide, methyl bromide. Methyl iodide seems to be the most carcinogenic, and also uses RP and I2 for manufacture but I also seen that it can be done with KI maybe? While searching for chloromethane I received mainly DCM stuff. Methyl bromide, or bromomethane is used as a soil fumigant, and should be easy to acquire. Can someone clue me in on whether the methyl halides really work, or if there is an easy way to make any of them?
--Word on the street is, You Reap What You Sow
(Active Asperger Archivist)
12-11-03 17:50
No 476273
yes, KI can be used for the synthesis of MeI. It's one of the rxns referenes in Org. Synth. Coll. Vol. under the synthesis of MeI.
Act quickly or not at all.
(Hive Bee)
12-11-03 18:33
No 476283
Thanks, It can be made from MeSO4 and KI, and supposedly can be made from methanol and KI. Interestingly enough, chloromethane can be made from methanol and Hcl, I am not sure of all this though, does anyone know if the mrthyl halides work for what I have in mind?
--Word on the street is, You Reap What You Sow
(Hive Bee)
12-11-03 19:29
No 476294
Just to clarify my stupidity, I am a bit confused which of the following (if any) is N-benzylidene alanine methyl ester.
either -
(1) Bz-CH=N-CH(C)-CO2Me or...
(2) Bz-CH2-N=C(C)-CO2Me
hoping its the first one - therfore giving the route from phenylalanine, by forming the ester, then the imine, alkalation, decarboxyation
(Wizard Master)
12-12-03 01:08
No 476353
(1) Bz-CH=N-CH(C)-CO2Me
Bz-CHO + H2N-C ==> Bz-CH=N-C + H2O
(Hive Bee)
07-11-04 23:40
No 518821
Lucid_ Dreamer did you ever get the article ....
A practical asymmetric synthesis of a-methyl a-amino acids using a chiral Cu–salen complex as a PTC
DOI:10.1016/S0040-4039(00)01247-8
Abstract
The asymmetric C-alkylation of N-benzylidene alanine methyl ester has been achieved using a copper(II) (salen) complex as an asymmetric phase transfer catalyst and provides a practical synthesis of a-methyl a-amino acids with up to 86% enantiomeric excess.
Tetrahedron Letters
Volume 41, Issue 37 , September 2000, Pages 7245-7248
also did you have any success in alkylating the alpha carbon of Phenylalanine, followed by decarboxylation to amph?.......java
Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
(Hive Bee)
07-12-04 05:19
No 518889
Why don't you just buy alpha-methyl-phenylalanine? A quick google search turns up hundreds of suppliers. It isn't watched or suspicious.