Galactose nitrone
1 was elaborated to several new 6-position modified thioalkyl-lincosamines.
A general method for the synthesis of 6-position modified lincosamines via stereospecific nucleophilic ...addition to readily available galactose 6-nitrone has been developed. A new route for the stereospecific installation of thioalkyl groups at the 1-position was also developed. These methods allow access to a variety of new derivatives of antibacterial lincosamides.
An efficient and stereospecific approach to the synthesis of structurally constrained aza-, oxa-, and thiabicyclo3.1.0hexane heterocycles has been achieved through application of the intramolecular ...cyclopropanation reaction of diazoacetates. The various constrained heterocycles (X = N, O, or S) are conveniently prepared from a common diol intermediate accessible from readily available cinnamyl alcohols. Application of the methodology to the synthesis of conformationally constrained oxazolidinone antibacterials is also discussed.
A new series of oxazolidinone analogs bearing unsaturated sulfur-containing C-rings is described. New synthetic approaches to the dihydrothiazine ring system are also disclosed.
A new series of ...antimicrobial oxazolidinones bearing unsaturated heterocyclic C-rings is described. Dihydrothiopyran derivatives were prepared from the saturated tetrahydrothiopyran sulfoxides via a Pummerer-rearrangement/elimination sequence. Two new synthetic approaches to the dihydrothiazine ring system were explored, the first involving a novel trifluoroacetylative-detrifluoroacetylative Pummerer-type reaction sequence and the second involving direct dehydrogenation of tetrahydrothiopyran S,S-dioxide intermediates. Final analogs such as 4 and 13 represent oxidized congeners of recent pre-clinical and clinical oxazolidinones.
An efficient solid phase synthesis of diverse pyridines and pyrido2,3-dpyrimidines is described. O-Immobilized keto esters
2 react with aldehydes to afford Knoevenagel derivatives
3. These undergo ...Hantzsch-condensation with α-oxo enamines to generate 1,4-dihydropyridines
4 that are oxidized with CAN to produce immobilized pyridines
5. The method has been extended to synthesis of fused pyrido2,3-dpyrimidines employing 6-aminouracils as the α-oxo enamine component. The course of the reaction on solid phase was studied by gel-phase
13C NMR spectrosopy. The synthesis is designed to be amenable for combinatorial libraries preparation.
Graphic
Oxazolidinone analogs bearing substituted piperidine or azetidine C-rings are described. Analogs with a methyl group at the 3-position of the azetidine ring or the 4-position of the piperidine ring ...exhibited reduced mitochondrial protein synthesis inhibition while retaining good antibacterial potency.
Oxazolidinone analogs bearing substituted piperidine or azetidine C-rings are described. Analogs with a methyl group at the 3-position of the azetidine ring or the 4-position of the piperidine ring exhibited reduced mitochondrial protein synthesis inhibition while retaining good antibacterial potency.
The synthesis and biological activities of novel conformationally constrained oxazolidinone antibacterials are described.
A new class of oxazolidinone antibacterials incorporating oxygen-, nitrogen-, ...or sulfur-containing heterobicyclic C-rings is described. The in vitro potency and in vivo efficacy of these conformationally constrained oxazolidinone analogs are discussed.
Combinatorial libraries of
N-acylated 5-(
S)-aminomethyloxazolidinone derivatives of
S-oxide and
S,
S-dioxide tetrahydro-4(2H)-thiopyranyl and thiomorpholine phenyloxazolidinone series have been ...synthesized on a solid phase and evaluated for antimicrobial activity. Several novel potent leads have been identified, including orally active oxazolidinones with enhanced activity against respiratory tract infection pathogens
Haemophilus influenzae and
Moraxella catarrhalis.
A series of new leads have been identified, including orally active compounds with enhanced potency against fastidious gram-negatives.
An efficient solid phase synthesis of chiral quinazolinediones is described. Immobilized amino acid based urea derivatives
3 undergo a racemization-free heterocyclization upon gentle heating in ...presence of tetramethylguanidine to afford fused pyrimidine-2,4-diones
6, which are smoothly N
1-alkylated under mild conditions to produce immobilized quinazolinediones
8. The method is amenable to combinatorial synthesis and offers broad scope for structural and chemical diversity, as illustrated by preparation of fused thieno2,3-dpyrimidine-2,4-dione
10 and hydroxamate pharmacophore bearing quinazolinedione derivative
11.
Graphic
An efficient solid-phase synthesis of 3,1-benzoxazine-4-ones is described. Immobilized amino acid based functionalized urea derivatives 2 undergo a high yielding heterocyclization under mild ...conditions in presence of coupling reagents (DIC, TsCI/Py, or Ac sub(2)O) to afford 3,1-benzoxazine-4-ones 6. The method offers broad scope for structural and chemical diversity, and is amenable for combinatorial synthesis of 3,1-benzoxazine-4-ones libraries with potential for discovery of novel serine protease inhibitors.
Solid-Phase Synthesis of β-Sultams Gordeev, Mikhail F; Gordon, Eric M; Patel, Dinesh V
Journal of organic chemistry,
11/1997, Letnik:
62, Številka:
23
Journal Article
Recenzirano
Solid-phase synthesis of β-sultams amenable for construction of sulfonyl β-lactam analogue combinatorial libraries is reported. Imine intermediates generated from polymer-immobilized amino acids and ...aldehydes are reacted with (chlorosulfonyl)acetates in the presence of pyridine to afford the solid-phase-tethered β-sultam products. The latter can be released from support by acidic cleavage (TFA) or photocleavage, depending on the nature of the linker employed (acid-labile or photolabile linkers). Immobilized 4-(9-fluorenyl)methoxycarbonyl β-sultams are further functionalized on supports to afford, upon cleavage, the respective carboxy and amido thiazetidine derivatives. The method can be employed in production of β-sultam libraries for identification of new antibacterial agents.
