Abstract
xi
Hexahydrobenzophenanthridines and their homologues 1 (n = 1, 2) constitute structural motifs of many biologically active compounds, such as dihydrexidine, A- 86929 and SCH 39166 (Figure 1). Dihydrexidine and A-86929 act as dopamine D1 agonist and SCH 39166 is a well known dopamine D1 antagonist, these are developed for the possible treatment of many neurological disorders like Parkinson’s disease, schizophrenia and obesity. Pictet-Spengler cyclization of the 2-Amino-1-aryltetralins 2 is known to afford hexahydrobenzophenanthridines. Thus, an efficient
enantioselective synthesis of trans-2-amino-1-aryltetralins 2 has been achieved via bis-oxazoline-Cu(OTf)2 catalyzed one-pot aziridination and regioselective intramolecular Friedel-Crafts cyclization of in situ generated aziridines 3 from 2- arylethyl styrenes 4 and PhINSO2(4-NO2C6H4) (aziridoarylation reaction). This catalytic and enantioselective aziridoarylation reaction has been employed for the asymmetric synthesis of A-86929 and dihydrexidine with overall yield of 56% and 17%, respectively. SCH 39166 was synthesized using similar protocol with overall yield of 33%. The asymmetric synthesis of trans-3-amino-4-aryltetrahydroquinolines were also achieved with high diastereo- (>99:1) and enantioselectivity (up to 90% ee) from N-cinnamylanilines via two steps protocol of enantioselective aziridination and intramolecular Friedel-Crafts cyclization of isolated chiral aziridines.
NH HO
HO
Dihydrexidine
NH RO
RO
S
R = H; A-86929 R = Ac; Adrogolide
NH
2
HO Cl SCH 39166 Ar
NHR
Ar NR
Ar
Z Z Z
2 3 4
NH
Ar Z
1
n n = 1, 2
Figure 1
Key words: Hexahydrobenzophenanthridines; Catalytic; Enantioselective; Aziridine;
Friedel-Crafts cyclization; trans-2-Amino-1-aryltetralins; Cu(OTf)2; Bis-oxazoline;
Dopamine D1 agonists; Dopamine D1 antagonist; Dihydrexidine; A-86929; SCH 39166; trans-3-Amino-4-aryltetrahydroquinolines.
