Synthesis, Stereochemical Confirmation, and Derivatization of 12(S),16ϵ‐Dihydroxycleroda‐3,13‐dien‐15,16‐olide, a Clerodane Diterpene That Sensitizes Methicillin‐Resistant Staphylococcus aureus to β‐Lactam Antibiotics

Abstract

Over the past decades, antibiotic resistance has grown to a point where orthogonal approaches to combating infections caused by resistant bacteria are needed. One such approach is the development of nonmicrobicidal small molecules that potentiate the activity of conventional antibiotics, termed adjuvants. The diterpene natural product 12(S),16ɛ-dihydroxycleroda-3,13-dien-15,16-olide, which we refer to as (À )-LZ-2112, is known to synergize with oxacillin against methicillinresistant Staphylococcus aureus (MRSA). To explore this activity, (À )-LZ-2112 was synthesized and the structure confirmed through X-ray analysis. Preliminary structure-activity relationship studies following the synthesis of several analogs identified key structural elements responsible for activity and indicate that scaffold simplification is possible. A preliminary mode of action study suggests mecA plays a role in the adjuvant activity of (À )-LZ-2112.

DBDMH-Promoted Methylthiolation in DMSO: A Metal-Free Protocol to Methyl Sulfur Compounds with Multifunctional Groups

“…However, as an unexpected result, a thioether structure instead of the sulfoxide group was found (Scheme 2). It is worth noting that different 2(5H)-furanone compounds have been developed in many fields such as modern organic synthesis [44], drug molecular design [45] and natural product total synthesis [46] due to their potential high biological activities, such as antiviral [47] or anti-HIV activity [48]. In particular, the thioetherified 2(5H)-furanone can be a kind of potential drug molecule with good anticancer activity, as Li's group reported before [49].…”