Asymmetric Total Synthesis of Onoseriolide, Bolivianine, and Isobolivianine

Abstract

In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.

Total Syntheses of Sarcandrolide J and Shizukaol D: Lindenane Sesquiterpenoid [4+2] Dimers

“…Inspired by our biomimetic total synthesis of bolivianine, [13] we began to consider a modified biosynthesis with cycloaddition between an either electron-normal or electrondeficient dienophile (10) and an electron-rich diene conjugated with a furan (11; Figure 1 d). Biogenetically, both diene and dienophile could be formed from natural lindenane precursors bearing a furan ring, such as lindenene (9) and its natural analogues.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…Palladium-catalyzed three-component coupling of tosylhydrazones, aryl halides, and norbornene led to functionalized norbornenes [1149]. A tosylhydrazone-derived palladium carbene complex undergoing a M a n u s c r i p t 145 cyclopropanation was a key step in the total synthesis of onoseriolide, bolivianine, and isoboloivianine [1150].…”

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

“…Herein we highlight Liu’s successful execution of this idea resulting in a highly concise route to 68 and 69 from verbenone. 99,100 …”

“…102 More commonly utilized metals in diazo-based cyclopropanation chemistry, 103 such as rhodium and copper, were less effective for this transformation. 99 Following deketalization (cat. TsOH, Me 2 CO), the ketone formed engaged the TES-protected pyruvate derivative shown in an aldol condensation, and following treatment with strong acid, furan 77 was formed.…”

“…In parallel studies, it was found that 80 cyclizes to 68 at ambient temperatures. 99 Overall, only 12 and 14 steps were needed to access 68 and 69 respectively, and the choice of verbenone, along with knowledge of its fragmentation chemistry, were crucial in this regard. 101 Aside from giving credence to a pericyclic-based biogenesis of 68 , 104–106 this work once again shows the unquestionable power of the Diels-Alder reaction in the rapid assembly of complex polycyclic molecules.…”