Shortest Enantioselective Total Syntheses of (+)-Isolaurepinnacin and (+)-Neoisoprelaurefucin

Abstract

The shortest enantioselective total syntheses of (+)-isolaurepinnacin and (+)-neoisoprelaurefucin have been accomplished. These syntheses were based on a common parallel synthetic strategy using Prins–Peterson cyclization in their core construction. In only one step, a seven-membered ring oxacycle with the correct cis -stereochemistry ring closure and the Δ 4 position of the endocyclic double bond in (+)-isolaurepinnacin was obtained. This unsaturation was also necessary to accede to the bromodioxabicycle on (+)-neoisoprelaurefucin.

Advancements in the synthesis of polyoxygenated oxepanes and thiepanes for applications to natural products

“…196 These sesquiterpene endoperoxides possess an unprecedented scaffold and have been infamously challen-Scheme 68 Synthetic routes to the oxepane cores in the syntheses of (+)-isolaurepinnacin and (+)-neoisoprelaurefucin. [187][188][189]192,193 ging target molecules, as one must take necessary precautions when constructing the peroxide on a large scale. Since its isolation in 1979, artemisinin (5) and its derivatives became target molecules for many groups.…”

“…In 2022, Sinka and coworkers developed the shortest known enantioselective total syntheses of (+)-isolaurepinnacin ( 496 ) and (+)-neoisoprelaurefucin ( 503 ) to date. 193 The cis -oxepane ring was constructed using a Prins–Peterson cyclization of chiral silyl alcohol 505 with chiral aldehyde 506 promoted by iron( iii ) bromide to afford 507 in a 58% yield, which was advanced to 496 in only 6 additional steps (Scheme 68). Beginning with the opposite enantiomer of silyl alcohol 505 the same Prins–Peterson cyclization with aldehyde 506 affords 508 that can be advanced to 503 in 8 additional steps (Scheme 68).…”

Síntesis de éteres cíclicos naturales

“…síntesis de los lauroxanos naturales (+)-isolaurepinnacino ( 27) y (+)-neoisoprelaurefucino (28) (Figura 21). 53 Figura 21. a) Síntesis de oxepenos mediante ciclación silil-Prins, b) síntesis enantioselectiva de (+)-isolaurepinnacino, c) síntesis enantioselectiva de (+)-neoisoprelaurefucino…”

Stereoselective Entry into α,α’‐C‐Oxepane Scaffolds through a Chalcogen Bonding Catalyzed Strain‐Release C‐Septanosylation Strategy

“…Some notable examples include rogiooloxepane A, isoprelaurefucin, Regiolenyne A and Nakorone. Surprisingly, only entropically less favored macrocyclization approaches, [21] such as ring‐closing metathesis (RCM), [19a] Prins‐Peterson cyclization, [19e] mercury catalyzed iodocyclization [22] or organocatalytic [23] macrocyclic ring closure methods (Figure 1C, left) were actively developed to gain entry into such oxepano‐scaffolds. However, the practical difficulties of such macrocyclizations are conspicuous.…”