Stereoselective Synthesis of cis-and trans-3-Amino-4-chromanols

• Published in: Chemical & pharmaceutical bulletin Vol. 25; no. 5; pp. 859 - 866
• Main Authors: SUGIHARA, HIROSADA, SANNO, YASUSHI
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 1977; Japan Science and Technology Agency
• Subjects: Adrenergic beta-Agonists - chemical synthesis; Benzopyrans - chemical synthesis; Chemical Phenomena; Chemistry; Chromans - chemical synthesis; Chromans - pharmacology; Stereoisomerism; β2-stimulant
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.25.859

3-Alkylamino-(cis-1a-c) and trans-1a-c), 7-hydroxy-3-isopropylamino-(cis-1d and trans-1d), 7, 8-dihydroxy-3-isopropylamino-(cis-1e and trans-1e) and 6, 7-dihydroxy-3-isopropylamino-4-chromanol (cis-1f) were synthesized. By the use of lithium cyanoborohydride (LiBH3CN), the reductive N-alkylation of 3-amino-4-chromanones with acetone proceeded smoothly to produce 3-isopropylamino-4-chromanones (12e and 12f) in good yields. Stereoselective hydrogenation of 4-chromanones in a basic or an acidic medium to give trans- or cis-aminoalcohols was discussed on the basis of the thermodynamic stability of the end products. Among the compounds synthesized, 7, 8-dihydroxy derivatives showed a strong β2-stimulating activity, whereas the 6, 7-dihydroxy congener was devoid of the activity. The results suggest an important role of the spatial arrangement of functional groups in these catecholamine molecules with regard to their pharmacological properties.