Stereodivergent total synthesis of Br-nannocystins underpinning the polyketide (10R,11S) configuration as a key determinant of potency

From Target-Oriented to Motif-Oriented: A Case Study on Nannocystin Total Synthesis

“…Though each approach is uniquely creative, certain approaches turn out more convenient for structural variation. Based on a robust Heck macrocyclization [ 5 ], we have been able to conduct systematic SAR study [ 15 , 16 , 17 ]. Meanwhile, having succeeded in a macrolactamization strategy [ 7 ], He et al later opted for our Heck macrocyclization approach in a subsequent SAR study [ 18 ].…”

“…No 8 Z -isomer could be detected by NMR in the crude reaction mixture. Marked by a Heck-type macrocyclization, this route has since served a valuable conduit for systematic SAR research [ 15 , 16 , 17 , 18 ].…”

Intramolecular Heck Reaction in Total Synthesis of Natural Products: An Update

“…in 2016 (Scheme 23) [67a] where precursor 227 was subjected to Heck macrocyclization in the presence of Pd(OAc) 2 , Cs 2 CO 3 , Et 3 N in DMF to yield nannocystin A in 58 % yield. The same group in 2019 adopted a similar approach for the successful construction of Br‐nannocystin and its different analogues [67b] …”

Site-directed late-stage diversification of macrocyclic nannocystins facilitating anticancer SAR and mode of action studies

“…22 Its marked anticancer potency coupled with a large ring feature warrants systematic SAR exploration. 19,[23][24][25][26] As discussed above, these diversityoriented syntheses have oftentimes been encumbered by the entropy-disfavored macrocyclization step. To raise the overall efficiency, late-stage diversification is preferred in that macrocycle formation precedes divergent synthesis.…”