Amino Diol Based Asymmetric Syntheses of a Fused Benzazepine as a Selective D1 Dopamine Receptor

Abstract

A six-step practical synthesis of (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H-benzo[d]naphtho-[2,1-b]azepin-12-ol, a selective D1 dopamine receptor, is developed starting from (1S,2S)-phenyl-2-amino-1,3-propanediol. An acid-promoted stereo-and regioselective cyclization of the benzazepine ring was established. Three double reactions in which two functional groups are transformed in a single step were developed. These include the double hydrolysis, the double reduction, and the cyclization and demethylation. The use of practical and economical reagents reduced the cost significantly.

Catalytic asymmetric aminolactonization of 1,2-disubstituted alkenoic acid esters: Efficient construction of aminolactones with an all-carbon quaternary stereo-centre

“…The aminolactones are valued enough to access several synthetic targets. [8][9][10] Herein we report the catalytic and enantioselective aminolactonization of internal b,gand g,d-alkenoic acid esters that provides g and d-lactones, respectively, containing internal amino functionality with high diastereo-(dr 4 99 : 1) and enantio-selectivity (ee upto 94%) and also synthesis of aminolactones having an all-carbon quaternary stereo-centre with excellent diastereo-(dr 4 99 : 1) and enantioselectivity (ee upto 98%).…”

“…The aminolactones are important structural motifs that are present in, or are precursors to, many biologically important compounds. 8,9 For example, aminolactones 3 can be easily transformed into b-benzyl-b-amino acids (Scheme 5), which are the key precursors to many compounds. 9 As an application, aminolactone 3g was converted to b-amino acid by reductive lactone opening.…”

Effects of fused benzene rings on tautomerizations and inversions of benzo, azabenzo, and oxabenzocycloheptatrienes at theoretical levels

“…Apparently, several derivatives of A X X X X X X Scheme 2 Tautomerization of three series of benzocycloheptatrienes (nB X ) to their corresponding tricyclic benzonorcaradienes (nTX) for n = 1-3; and X = CH 2 , NH, and O; B = bicyclic; T = tricyclic azabenzocycloheptatrienes are considered as pharmacologically important molecules [16]. For example derivatives of 7H-7-azabenzocycloheptatriene serve as selective D 1 dopamine receptors and are useful in the treatment of psychose, depression, pain, and D 1 -dependent neurological disorders [17][18][19][20]. Similarly, derivatives of oxabenzocycloheptatrienes occur in natural products [21,22] and are used as natural herbicides [23].…”

“…Similarly, derivatives of oxabenzocycloheptatrienes occur in natural products [21,22] and are used as natural herbicides [23]. Hence, studying tautomerization and inversions of these biologically and pharmacologically interesting compounds provides an opportunity to disclose new aspects of their structural behavior [16][17][18][19][20][21][22][23][24][25][26][27][28].…”

Sodium Triacetoxyborohydride

“…11 (F) It is shown that STAB-H effectively reduced amide 14 to 15 in the total synthesis of a selective D1 antagonist useful in the treatment of psychoses, depression, and D1-dependent neurological disorders. 12 (G) Cleavage of oxazolidines 16 can easily be carried out with STAB-H 13 to provide 17 and this tactic was featured in the first enantiospecific synthesis of salinosporamide A. 14…”