A Cyclopropanol-Based Strategy for Subunit Coupling:  Total Synthesis of (+)-Spirolaxine Methyl Ether

Abstract

A strategy for ketone synthesis with cyclopropanols as intermediates and its application to (+)-spirolaxine methyl ether is described. The synthesis also features an application of Fu's alkyl-alkyl Suzuki coupling.

Nickel-catalyzed cross coupling of non-activated alkyl halides: a mechanistic perspective

“…Fu et al applied Ni-catalyzed Negishi coupling for the formal synthesis of a-cembra-2,7,11-triene-4,6-diol 63 and Fluvirucinine A1. 49 Phillips et al employed Pd-catalyzed alkyl-alkyl Suzuki coupling for the total synthesis of (+)-Spirolaxine methyl ether 90 and Pyranicin. 91 With the increasing awareness of the synthetic community of these new coupling methodologies, the cross coupling of non-activated alkyl halides is expected to become a standard tool in organic synthesis, benefiting the production of synthetic building blocks, fine and speciality chemicals, agro-chemicals, biologically and pharmaceutically active molecules, and organic materials.…”

Enantioselective Iridium‐Catalyzed Phthalide Formation through Internal Redox Allylation of Phthalaldehydes

“…The assignment of absolute stereochemistry for adducts 3a–3t was made in analogy to phthalide 3l , which was determined by single crystal X-ray diffraction, and phthalide 3t , which was evaluated by comparison of its optical rotation to that of an authentic sample. [16] Underscoring the utility of this method in target oriented synthesis, the preparation of 3t constitutes a formal synthesis of two different phthalide natural products: ent -spirolaxine methyl ether [17] and CJ-12,954 (Figure 2). [18] Both compounds have been shown to exhibit antibiotic activity against the Gram-negative bacteria Helicobacter pylori .…”

sp3-sp3 Coupling reactions in the synthesis of natural products and biologically active molecules

“…In 2007 the group based their total synthesis of the polyketide (+)-spirolaxine methyl ether (17) on a late stage alkylalkyl Suzuki cross-coupling key step. 12 The class of the spirolaxines are produced by the white-rod fungi Sporotrichum and Phanerochaetei and show potential as antibiotics against Helicobacter pylori. Additionally, it was reported that (+)-spirolaxine methyl ether (17) inhibits the growth of multiple cell lines and lowers cholesterol levels.…”