The principal activity in the field of advanced medicinal and combinatorial chemistry is discovery of novel and potent synthetic methods to promote the preparation of compound libraries. Multicomponent reactions (MCRs), which consist of several simultaneous bond forming reactions allowing highly efficient synthesis of complex molecules starting from simple substrates in a one-pot manner, are powerful tools to approach this goal (1). Spirobenzothiazinechromans exhibit a wide range of pharmacological properties such as Antimicrobial, antimalarial, anti-inflammatory, antifungal and 15-lipoxygenase inhibition (2). Enzyme, as well known, is preferred to chemical catalyst because of its high effectiveness, high specificity and mild reaction conditions. Lipase (triacylglycerol acyl hydrolases) is a kind of ubiquitous enzymes with various biological activities, including enantioselective hydrolysis and esterification, chiral resolution, synthesis of enantioenriched monomers andmacromolecules for polymerization reactions, and other enzymatic reactions. Enzymes immobilized by magnetic microspheres could be separated easily and rapidly from the reaction system to enhance the reusability of enzyme (3). In this work we used nanobiocatalyst that synthesized in multicomponent reactions for synthesis of spirobenzothiazinechromans (4) and novel spirobenzothiazinechromans. we synthesized spirobenzothiazinechromans and novel spirobenzothiazinechromans in 45 minuts with high yield.