Rajarathnam E. Reddy

Asymmetric strecker synthesis using enantiopure sulfinimines: A convenient synthesis of α-amino acids

Abstract Diethylaluminum cyanide adds stereoselectively to enantiopure sulfinimines 1 and 2 to give diastereomerically enriched α-amino nitriles 3 and 4 which are hydrolyzed in one step to α-amino acids 5 in >95% ee and good yields.

Asymmetric synthesis of sulfinimines: Chiral ammonia imine synthons

Abstract Two Andersen-type procedures for the preparation of enantiopure sulfinimines 1 (R=H) in better than 95% ee from nitriles and aldehydes are described.

Collagen cross-links: Synthesis of pyridinoline, deoxypyridinoline and their analogues

Abstract An efficient chiral synthesis of (S,S)-(−)-3g, a key intermediate for the preparation of collagen cross-links pyridinoline (Pyd, 1) and deoxypyridinoline (Dpd, 2) was achieved from (4S)-5-(tert-butoxy)-4-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid (21b). Quaternization of (S,S)-(−)-3g with iodide (2S,5R)-(+)-4a followed by hydrolysis provided a first chiral synthesis of natural (+)-Pyd (1). 1-(2S)-(+)-Pyd (1) was also synthesized from (S,S)-(−)-3g and iodide (2S,5S)-(+)-4a. Similarly, quaternization of (S,S)-(−)-3g with iodide (2S)-(−)-4b, which was prepared from (2S)-(−)-6-amino-2-[(tert-butoxycarbonyl)amino]hexanoic acid (31) in three steps, followed by hydrolysis afforded natural (+)-Dpd (2) in 5.3% overall yield. Also, the synthesis of racemic Dpd [(±)-2] and a variety of its analogues is presented.

Approaches toward the total syntheses of astins A, B, and C

Two nonessential amino acids, (+)-(S)-2-aminobutanoic acid and the methyl ester of L-β-phenylalanine [(+)- (R)-3-amino-3-phenyl propanoic acid], were synthesized to provide a tripeptide which will be used in the total syntheses of astins A, B, and C.

Synthesis of (2R, 3S)-methyl-2-fluoro-3-(n-benzoylamino)-3-phenylpropanoate: Modified side chain of taxol

Abstract Methyl-2-fluoro-3-(N-benzoylamino)-3-phenylpropanoate 2 and 3 , fluorine analogs of the C-13 side chain of taxol, were synthesized by electrophilic fluorination of the dianion of methyl ( R )-(−)-(N-benzoyl)-3-amino-3-phenylpropanoale ( 4 ).

TOTAL SYNTHESIS OF (+)-DEOXYPYRROLOLINE : A POTENTIAL BIOCHEMICAL MARKER FOR DIAGNOSIS OF OSTEOPOROSIS

The collagen cross-link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an alpha-acetoxynitro compound with benzyl isocyanoacetate.

Synthesis of Arylglyoxylic Acids and Their Collision-Induced Dissociation

Abstract A variety of substituted arylglyoxylic acids (2a−g) were synthesized via oxidation of the corresponding aryl-methylketones (1a–e) using selenium dioxide or Friedel–Crafts acylation of phenol (3) with ethyl chlorooxoacetate and further transformations. It was found that the arylglyoxylic acids (2) undergo facile unimolecular dissociation with loss of carbon monoxide to give the corresponding arylcarboxylic acids (7) under collisionally induced mass spectrometric conditions.

Collagen cross-links: a convenient synthesis of tert-butyl-(2S)-2-[(tert-butoxycarbonyl)amino]-4-(2-oxiranyl)butanoate

Abstract An efficient synthesis of tert -butyl-(2 S )-2-[( tert -butoxycarbonyl)amino]-4-(2-oxiranyl) butanoate ( 5 ), the key intermediate for preparation of collagen cross-links (+)-pyridinoline (Pyd, 1 ) and (+)-deoxypyridinoline (Dpd, 2 ) was described from (4 S )-5-( tert -butoxy)-4-[( tert -butoxycarbonyl)amino]-5-oxopentanoic acid ( 6 ) in six steps. Also, an improved synthesis of iodide (2 S )-(−)- 4b was presented.

Nonproteinogenic amino acids: an efficient asymmetric synthesis of (S)-(−)-acromelobic acid and (S)-(−)-acromelobinic acid

Abstract An efficient synthesis of ( S )-(−)-acromelobic acid ( 1 ) and ( S )-(−)-acromelobinic acid ( 2 ) is described via asymmetric hydrogenation protocol. Asymmetric hydrogenation of dehydroamino acid derivative 23 using ( R , R )-[Rh(DIPAMP)(COD)]BF 4 catalyst followed by removal of the protective groups afforded ( S )-(−)-acromelobic acid ( 1 ) in >98% ee. The key intermediate 23 was prepared from citrazinic acid ( 8 ). The dehydroamino acid derivative 33 required for the synthesis of ( S )-(−)- 2 was prepared from 2,5-lutidine ( 27 ), which upon hydrogenation using ( S , S )-[Rh(Et-DuPHOS)(COD)]BF 4 catalyst afforded ( S )-(+)- 34 in 93% yield and >96% ee. Removal of protective groups in ( S )-(+)- 34 afforded ( S )-(−)-acromelobinic acid ( 2 ) in good overall yield.

Evaluation of chemiluminescent estradiol conjugates by using a surface plasmon resonance detector.

A series of chemiluminescent 17beta-estradiol probes were synthesized. Relative equilibrium dissociation constants (K(D)) for the interaction of an anti-E(2) Fab fragment for the probes in solution were evaluated using a single E(2)-analog biosensor surface on a BIAcore surface plasmon resonance instrument. The results show the antibody fragment binds all chemiluminescent conjugates tested with high affinity showing only minor preferences for site of substitution (C6 versus C7), stereochemistry (alpha versus beta), or linker moiety.