11-Step Total Synthesis of Araiosamines

Abstract

A concise route to a small family of exotic marine alkaloids known as the araiosamines has been developed, and their absolute configuration has been assigned. The dense array of functionality, high polarity, and rich stereochemistry coupled with equilibrating topologies present an unusual challenge for chemical synthesis and an opportunity for innovation. Key steps involve the use of a new reagent for guanidine installation, a remarkably selective C–H functionalization, and a surprisingly simple final step that intersects a presumed biosynthetic intermediate. Synthetic araiosamines were shown to exhibit potency against Gram-positive and -negative bacteria despite a contrary report of no activity.

Design, Synthesis, and Biochemical Evaluation of Alpha‐Amanitin Derivatives Containing Analogs of thetrans‐Hydroxyproline Residue for Potential Use in Antibody‐Drug Conjugates

“…[38] To prepare the guanidino analog 7, amanitin 6 was reacted with N-Boc-N'-TFA-pyrazole-1-carboxamidine in THF/DMSO in the presence of DIPEA. [39] The resulting doubly protected guanidine was treated with K 2 CO 3 in MeOH and H 2 O to remove the TFA protecting group, affording intermediate 9. Finally, the Boc protecting group was removed using TFA in DCM (1 : 1) to yield an amanitin analog 7, containing a guanidino-proline residue (Figure 6C).…”

Applications oftert-butanesulfinamide in the synthesis of N-heterocyclesviasulfinimines

“…The total synthesis of araiosamines, a group of marine alkaloids with 3 indole and 2 guanidine units has been established via an 11-step process from Baran's lab. 45 The synthetic protocol provided with the racemic forms of the target compound and hence to assign the absolute conguration, synthesis of the natural enantiomer was attempted. The synthesis began with a Mannich reaction involving chiral sul-nimine 232 to render the desired Mannich product 234 as a mixture of diastereomers in the ratio 7 : 1:2 : 0.5 (Scheme 39).…”

Hydrozirconation of C=X Functionalities with Schwartz's Reagent

“…Baran and co-workers [49] demonstrated the reduction of nitrile function to aldehyde by [Cp 2 Zr(H)Cl] (Scheme 41). This transformation was applied in a one of 11-steps of total synthesis of family of araiosamine alkaloids.…”