59865-23-5Relevant academic research and scientific papers
N-Methylative aziridine ring opening and asymmetric synthesis of MeBmt
Kim, Yongeun,Yoon, Doo-Ha,Ha, Hyun-Joon,Kang, Kyung Yeon,Lee, Won Koo
, p. 5918 - 5920 (2011/11/29)
Asymmetric synthesis of MeBmt, an unusual amino acid constituent of cyclosporine A, was achieved from aziridine-(2R)-carboxaldehyde through the highly stereoselective addition of (E)-crotylboronate and the subsequent N-methylative aziridine ring opening as key steps.
A short synthesis of the unusual amino acid of cyclosporine (4R)-4-[(E)-2-butenyl]-4,N-dimethyl-L-threonine (MeBmt)
Savignac,Durand,Genet
, p. 717 - 722 (2007/10/02)
MeBmt 1 was prepared in four steps from the optically pure (2Z, 4R) 4-methyloct-6-yn-2-en-1-ol 8, Z allylic alcohol containing an alkynyl group at the γ position. The two stereogenic centers C-2 and C-3 in the product were controlled using Sharpless' epoxidation and subsequent ring opening at C-2 of the epoxy acid 10 with methylamine.
N-(9-Phenylfluoren-9-yl)-α-amino Ketones and N-(9-Phenylfluoren-9-yl)-α-amino Aldehydes as Chiral Educts for the Synthesis of Optically Pure 4-Alkyl-3-hydroxy-2-amino Acids. Synthesis of the C-9 Amino Acid MeBmt Present in Cyclosporin
Lubell, William D.,Jamison, Timothy F.,Rapoport, Henry
, p. 3511 - 3522 (2007/10/02)
Serine derived N-(9-phenylfluoren-9-yl)-α-amino ketones were prepared by acylation of primary organometallic reagents with amino acid isoxazolidides.When the amino and hydroxyl functions of serine were constrained in oxazolidine and oxazolidinone rings, alkylation of these ketones as their lithium enolates proceeded regiospecifically with good to excellent diasteroselectivity.Reduction of the oxazolidine and oxazolidinone ketones diastereoselectively led to N-protected 4-alkyl-branched 2-amino 1,3-diols that were subsequently oxidized in two steps, via the N-(9-phenylfluoren-9-yl)-α-amino aldehyde, to produce 4-alkyl-β-hydroxy-α-amino acids.In this way L-(+)-MeBmt (1), the C-9 amino acid of cyclosporin, and its D-(-) enantiomer were prepared in 12 steps from D- and L-serine, respectively, with 22percent overall yield and >99percent enantiomeric purity.N-(9-Phenylfluoren-9-yl)-MeBmt triple-bond and 6Z double-bond analogues 37 and 39 were also prepared.This synthetic route requires only a single chiral source (serine) and provides for configurational choice at all four diastereomeric centres.
Radical Cyclization in Stereospecific Introduction of Chirality at "Off Template Site" of 1,2-O-Isopropylidene-α-D-xylo-hexofuranose
Rao, A. V. Rama,Yadav, J. S.,Rao, C. Srinivas,Chandrasekhar, S.
, p. 1211 - 1213 (2007/10/02)
Bromoacetals derived from 5,6-dideoxy-1,2-O-isopropylidene-α-D-xylo-hex-5-ynofuranose (9) undergo facile free radical cyclization leading to the formation of olefinic acetals which are chemically manipulated to introduce either of the chiralities at C-5 of α-D-hexofuranose.
HIGHLY STEREOSELECTIVE APPROACH FOR β-HYDROXY-α-AMINO ACIDS FROM D-GLUCOSE : THE SYNTHESIS OF MeBmt
Rao, A.V. Rama,Yadav, J.S.,Chandrasekhar, S.,Rao, C. Srinivas
, p. 6769 - 6772 (2007/10/02)
A highly stereoselective protocol for the synthesis of β-hydroxy-α-amino acids from glucofuranose has been developed which has culminated in stereospecific synthesis of MeBmt - an unusual aminoacid component of immunosuppressive peptide cyclosporin.
A STEREOSPECIFIC SYNTHESIS OF (4R)-4--4,N-DIMETHYL-L-THREONINE (MeBmt)
Rao, A. V. Rama,Dhar, T. G. Murali,Chakraborty, T. K.,Gurjar, M. K.
, p. 2069 - 2072 (2007/10/02)
The utility of readily obtainable cis-oxazolidinone derivative (14) has been explored for the efficient and stereospecific synthesis of (4R)-4--4,N-dimethyl-L-threonine, an unusual syn-β-hydroxy-α-amino acid of cyclosporine.
A Short Synthesis of Enantiomerically Pure (2S,3R,4R,6E)-3-Hydroxy-4-methyl-2-(methylamino)-6-octenoic Acid, the Unusual C-9 Amino acid Found in the Immunosuppressive Peptide Cyclosporine
Aebi, Johannes D.,Dhaon, Madhup K.,Rich, Daniel H.
, p. 2881 - 2886 (2007/10/02)
A new and efficient synthesis of enantiomerically pure (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (MeBmt, 2) is reported.Reaction of (2R,4E)-2-methyl-4-hexenal (6c) with p-methoxybenzyloxycarbonylsarcosine tert-butyl ester (Pmz-Sar-O-t-Bu, 5) gave MeBmt (2) in 18-20percent overall yield.The lithium enolate of the tert-butyl ester is more stable than the corresponding methyl ester at higher temperature (room temperature vs. -78 deg C) and reacts selectively with aldehydes even in the presence of impurities.Room temperatures conditions were needed in order to increase the desired anti-Cram product 9a.The Pmz group proved superior to other amino protecting groups (e.g., Cbz) because residual Pmz-sarcosine derivatives could be easily removed from products 9a and 9b by cleavage of the Pmz group by reaction with TFA/anisole.This procedure eliminated the need for column chromatography after the aldol reaction.Reaction of the lithium enolate of Pmz-Sar-O-t-Bu (5) with aldehyde 6c afforded only the two trans-substituted 2-oxazolidinones 9a and 9b and none of the cis-substituted 2-oxazolidinones.The chemically pure diastereomeric mixture of 2-oxazolidinones 9a and 9b was resolved by using (1S,2R)-(+)-ephedrine to give enantiomerically and diastereomerically pure 9a in 18-20percent overall yield (from aldehyde 6c).Hydrolysis of 9a gave the desired MeBmt (2) in quantitative yield.This amino acid was incorporated into cyclosporin A (CSA, 1) by known literature procedures.In order to demonstrate that the synthetic methodology described in this paper can be utilized in the synthesis of a number of MeBmt (2) analogues, 1'-desmethyl-2-oxazolidinone 10a was also prepared by similar procedures.
