Combinatorial synthesis of natural product-like molecules using a first-generation spiroketal scaffold.
Recently, significant attention has been focused on the synthesis small-molecule libraries based on natural product or natural product-like structures. In this paper, we report our initial studies on the use of the 1,7-dioxaspiro[5,5]undecane (spiroketal) moiety as a rigid-core template for elaboration using parallel synthesis techniques. The synthesis of a spiroketal scaffold that is reminiscent of the spiroketal subunits found in the spiroketal macrolide antibiotics will be described. Elaboration of three independently addressable functional groups on the scaffold using solution-phase parallel synthesis techniques led to the preparation of a small library of natural product-like compounds. These studies pave the way for evaluation of highly functionalized spiroketals in phenotypic assays and as prospective antagonists of protein-protein interactions.
Kulkarni
Bheemashankar A
BA
Department of Chemistry and Center for Streamlined Synthesis, Metcalf Center for Science and Engineering, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
Roth
Gregory P
GP
Lobkovsky
Emil
E
Porco
John A
JA
D000447:Aldehydes / Q000737:chemistry; D001685:Biological Factors / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018716:Molecular Mimicry; D013141:Spiro Compounds / Q000737:chemistry
D000447:Aldehydes; D001685:Biological Factors; D013141:Spiro Compounds