A facile synthesis of novel di-spiro compounds has been achieved via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to the conjugated double bond of andrographolide. When the amino acid was changed from sarcosine to l-proline, the product formation took a different course as determined by 2D NMR and X-ray crystallographic analysis. © 2010 Elsevier Ltd. All rights reserved.