The synthesis and biodistribution of 3‐(4′‐[¹²⁵I]‐iodophenyl)‐4‐aminobutyric acid, a radioiodinated analogue of baclofen

Abstract

SUMMARYBaclofen has been found to bind to receptors in the central nervous system that are specific for 7-aminobutyric acid (GABA), a well known inhibitory neurotransmitter. This paper describes the synthesis of a radioiodinated analog of baclofen as part of an effort to develop receptor probes useful in single photon emission computed tomography. Prel imi nary biodis tr ibut ion studies showed the radioiodinationed analog to be essentially stable to in vivo deiodination and have a distribution profile similar to that of baclof en.

Synthesis of γ‐Aminobutyric Acid Analogs

“…Substrates were prepared in two steps from 2-aminoethanol derivatives (97). The conjugate addition of the arylboronic acid (98) was carried out in the presence of Rh(acac)(C 2 H 4 ) 2 , and (S)-2,2 0 -bis(diphenylphosphino)1,1 0 -binaphthyl (BINAP), affording the protected amino acid (R)-(100) in good yield and enantiopurity. Compound (100) can be converted to (R)-3 [89,90].…”

“…[96]. The synthesis of a wide range of baclofen analogs has also been described including the phosphonic analog, phaclofen [97], iodobaclofen [98], heterocyclic analogs [99,100], hydroxysaclofen [101,102], homologs [103][104][105][106], pyrolidinone analogs [107], and conformationally restricted derivatives [108,109]. A highly efficient three-step synthesis of the phosphonic analog of baclofen, (AE)-phaclofen (114a) [110] and its a,a-difluoro analog (114b) has been reported (Scheme 14.32) [111].…”

Eco-friendly conjugate hydrocyanation of α-cyanoacrylates using potassium hexacyanoferrate(II) as cyanating reagent

“…The resulting α,β-dicyanopropanoates are valuable intermediates for the synthesis of medicines and can be readily transformed into acids, esters, amides and amines (Rappoport, 1970). To date, many cyanating reagents have been used as additions to α,β-unsaturated esters, such as HCN (Griffiths et al, 1991), KCN (Aizencang et al, 1995;Sammelson et al, 2004), NaCN (Das et al, 2008;Rajib et al, 2012), TMSCN (Mazet & Jacobsen, 2008;Sammis et al, 2004), CNCOOEt (Wang et al, 2010) and acetone cyanohydrins (Wakita et al, 1990). However, some problems continue to be associated with the use of the existing cyanating reagents, including strong toxicity for KCN and NaCN, volatility for HCN, instability for acetone cyanohydrins, and moisture sensibility for TMSCN and CNCOOEt.…”