Short and efficient chiral pool and RCM approach towards the synthesis of the macrocyclic core of the salicylihalamides

Synthesis of Macrocyclic Compounds by Ring Closing Metathesis

“…In similar reactions Snider [36] and Georg groups [37] showed that substrate structures are very much important in RCM.…”

3 Transition metals in organic synthesis : Part (i) Catalytic applications

“…Ph 3 P᎐ ᎐ O or DMSO ruthenium level = 1-2 µg/5 mg of product; without added reagent, ruthenium level = 59.7 µg/5 mg product; theoretical amount of ruthenium at 5 mol% = 90 µg/5 mg of product) with the advantages that both Ph 3 P᎐ ᎐ O and DMSO are inexpensive and compatible with a wide range of functional groups. The method has been employed for removal of ruthenium byproducts in simple and complex molecules, such as 1,6-dienes and the macrocyclic core of the salicylihalamides, 164 respectively.…”

Facile Synthesis of Enantiopure 4‐Substituted 2‐Hydroxy‐4‐ butyrolactones using a Robust Fusarium Lactonase

“…As chiral building blocks, they have been widely used in the pharmaceutical industry for the production of ACE inhibitors1a such as Enalapril, Cilazapril, Benazepril etc. They are also used in the synthesis of natural products with antitumor or cytotoxic activities, including Apoptolidin,1b Epothilones,1c Salicylihal‐amides1d and Bengazoles 1e. Some of these lactones have been found to be human hunger modulators2 or exhibit significant antitumor and cytotoxic activities against cultures of P388 cells 3…”

“…Due to the great interest in their four stereoisomers, different strategies to make these chiral lactones have been developed. These include: a) chiral pool synthesis, using glucose,1d malic acid,1c xylose3 and so on; b) chiral auxiliaries, such as hydrazine SAEP4 and c) asymmetric catalysis, including enzymatic5 and non‐enzymatic routes 6. However, strategies a and b share common problems, such as expensive starting materials or auxiliaries and complicated synthetic routes 4,7.…”