A novel oxazine ring closure reaction affording (Z)-((E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)acetaldehydes and their anti-osteoclastic bone resorption activity

A novel oxazine ring formation method was established using the reaction of 2-acetyl-( E )-3-styrylcarbonylaminobenzo[ b ]furans ( 4 ) with Vilsmeier–Haack–Arnold reagent to afford ( E and Z )-(( E )-2-styrylbenzo[ b ]furo[3,2- d ][1,3]oxazin-4-ylideno)acetaldehydes ( 5 ). ( Z )-4-(8-Bromo-( E )-2-styrylbenzo[ b ]furo[3,2- d ][1,3]oxazin-4-ylideno)but-( E )-2-enoic acid ethyl ester ( 6b ), derived from ( Z )- 5a , showed significantly potent anti-osteoclastic bone resorption activity comparable to 17 β -estradiol (E 2 ).