185121-30-6

Upstream product

• 191406-16-3 (S)-2-(9-Phenyl-9H-fluoren-9-ylamino)-pentanedioic acid 1-methyl ester 

Downstream Products

• 191406-19-6 (5S)-5-acetyl-1-(9'-phenylfluoren-9'-yl)pyrrolidin-2-one 
• 191406-21-0 (S)-5-((S)-1-hydroxyethyl)-1-(9-phenyl-9H-fluoren-9-yl)pyrrolidin-2-one 

Relevant academic research and scientific papers

Enantiomerically Pure Highly Functionalized α-Amino Ketones from the Reaction of Chiral Cyclic N-(9-Phenylfluoren-9-yl) α-Amido Esters with Organolithium Reagents

The reaction of methyl N-(9-phenylfluoren-9-yl)pyroglutamate with several organolithium reagents afforded the corresponding ketones in excellent yields and with complete retention of enantiomeric purity. The success of this transformation is due to the unusual stability of the tetrahedral intermediates 5, which stems from two factors: the electron-withdrawing effect of the amide nitrogen and the lithium complexing ability of the fluorenyl ring of the 9-phenylfluoren-9-yl group. This ester-to-ketone transformation was also successfully applied to oxazolidinone 9 and imidazolidinone 20 and provided a ketone (21b) that was ultimately transformed into the urea-lactam 26 which incorporates the bicyclic core of streptolidine lactam, a component of the streptrothricin antibiotics.

Rigid dipeptide mimetics: Efficient synthesis of enantiopure indolizidinone amino acids

An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from L- and D-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of β-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric α,ω-bis[N-(PhF)amino]azelate δ-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl-2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric α,ω-bis[N-(PhF)amino]azelate δ-alcohol 7a, which upon mesylation and intramolecular S(N)2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]indolizidinone methyl ester 12 with NaN(SiMe3)2 and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation-activity relationships of various biologically active peptides.