Synthesis of Novel Heteroarotinoids with Receptor Activation Capabilities and Tgase Activity. Single Crystal Analysis of (E)-4-[(2,3-dihydro- 2,2,4,4,-tetramethyl-2H-1-benzo- [b]thiopyran-6-Yl)- 1-propenyl]-2-methylbenzoic Acid

Abstract The syntheses of ethyl (E)-4-[(2,3-dihydro-2,2,4,4-tetramethyl-2H-1-benzo[b]thiopyran-6-yl)-1-propenyl]-2-methylbenzoate (1) and (E)-4- [(2,3-dihydro-2,2,4,4-tetramethyl-2H-1-benzo[b]thiopyran-6-yl)-1-pro- penyl]-2-methylbenzoic acid (2) have been achieved. In comparison to ester 1, acid 2 exhibited greater efficacy in activating RARα, RARβ, and RARγ as well as greater potency in activating RARα and RARβ. Interestingly, both the ester 1 and acid 2 exhibited nearly equal potency in activating RARγ. Both compounds also induced tissue transglutaminase (TGase) activity approximately 50% of the level induced by trans-retinoic acid. An X-ray diffraction analysis of (E)- 2 revealed the aryl rings as nearly orthogonal [74, [2] ] and a torsional angle of 46.5(2)° between the thiochroman group and the propenyl group. Conjugation between such groups may not be a stringent requirement for receptor activation.