Woo-Baeg Choi

An efficient asymmetric synthesis of (R)-3-amino-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one

Abstract Two approaches for the asymmetric preparation of (−)- or (+)- α-aminobenzlactam 1 are described. One route is based on the asymmetric hydrogenation of enamide 5 and the other on the racemization/resolution of (±)- 1 .

Synthesis of functionalized furo[2,3-b]pyridines via the Pd-catalyzed coupling of acetylenes to iodopyridones. Preparation of a key intermediate to a new HIV protease inhibitor L-754,394

Abstract The synthesis of 1 was accomplished in 55% overall yield via the Pd-catalyzed coupling of 3 and 4 followed by Cu-catalyzed cyclization of the resulting intermediate 2.

A practical synthesis of the 5-chloromethyl-furo[2,3-b]pyridine pharmacophore

Synthesis of the furopyridine 2 was accomplished in 52% overall yield from 6-hydroxynicotinic acid (3). The synthesis is highighted by a Heck coupling of 5 with ethylene followed by an NCS mediated oxidative cyclization and elimination sequence.

A chemical synthesis of nicotinamide adenine dinucleotide (NAD

A practical synthesis of nicotinamide mononucleotide (β-NMN) and a high yield coupling with AMP-morpholidate that also provides NAD+ in an efficient manner are reported.

A stereoselective synthesis of a key 1β-methylcarbapenem intermediate via a diastereoselective decarboxylation

(3S,4S)-3[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-[(R)-1-carboxyethyl]-2-azetidinone 7a was prepared from (3R,4R)-4-acetoxy-3-[(R)-1-t-butyldimethylsilyloxy)ethyl]-2-azetidinone 3 via a sequence involving coupling with 2,2,5-trimethyl-1,3-dioxan-4,6-dione 4, N-silylation, solvolysis of the methylmeldrums acid moiety and a stereoselective acid catalyzed decarboxylation.

Practical synthesis of α-amino acids using cis-aminoindanol derived hippuric acid amide as a glycine enolate equivalent

Abstract The use of cis -aminoindanol as a chiral auxiliary for asymmetric synthesis of α-amino acids is described. Alkylation of the chirally modified glycine enolate 2 with a number of alkyl halides in the presence of lithium chloride gave the corresponding alkylated product in 90 ∼ 99% diastereoselectivity.

Asymmetric bioreduction of a bisaryl ketone to its corresponding (S) -bisaryl alcohol, by the yeast Rhodotorula pilimanae ATCC 32762

Abstract The screening of 310 microbial strains yielded eight as suitable biocatalysts for the asymmetric bioreduction of a highly hindered bisaryl ketone to its corresponding alcohols. The production of both enantiomers with elevated optical purity (ee>96%) was achieved by different microorganisms. When scaling up the asymmetric bioreduction process in laboratory bioreactors (23 l scale), the production of preparative amounts (1.5 g) of the ( S ) enantiomer with elevated optically purity (ee>96%) was achieved when employing the yeast Rhodotorula pilimanae ATCC 32762. Achieving this asymmetric bioreduction with enantiocomplementarity in employing such a hindered substrate is remarkable and highlights the potential of such biological approach.

Crystallization-induced asymmetric transformation: Stereospecific synthesis of L-768,673

Abstract A highly convergent, asymmetric synthesis of L-768,673, an I ks Class III antiarrythmic drug candidate, is described. Synthesis of the recemic 1-trifluoroethyl-3-amino-5-phenyl benzodiazepinone [(±)-amine] was achieved by Ru-catalyzed hydrogenation of the corresponding oxime that was derived from commercially available 1-trifluoroethyl-5-phenyl benzodiazepine in 76% overall yield. An efficient one-pot resolution-racemization of (±)-amine provided the desired (±)-amine as its mandelate salt in 92% yield and 99.4% ee. Regioselective ortho-lithiation of 1,3-bis(trifluoromethyl)benzene with n-BuLi in the presence of a catalytic amount of 2,2′,6,6′-tetramethylpiperidine afforded its aryl lithium. Subsequent transmetalation and alkylation with allyl bromide produced the corresponding olefin. Ru-catalyzed oxidative cleavage of the terminated double bond of the olefin provided the desired 2,4-bis(trifluoromethyl)phenylacetic acid in 35% overall yield. A modified Schotten-Baumman procedure was developed for coupling of (+)-amine and the acid to produce L-768,673 in 92% yield without racemization.

A stereoselective synthesis of a 2-functionalized-methyl-1β-methylcarbapenem key intermediate via decarboxylation

An efficient synthesis of a key intermediate 2a for the synthesis of 2-functionalized methyl-1β-methylcarbapenem antibiotics 1 has been realized via a stereoselective decarboxylation reaction.