A Radical Cascade Enabling Collective Syntheses of Natural Products

Abstract

Qin and co-workers use photocatalytic conditions to generate a nitrogencentered radical from aniline-type sulfonamide, which reverses the conventional reactivity between two electron-donating amine and enamine groups and initiates radical cascade reactions with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.

Strategies to diversify natural products for drug discovery

“…through two environmentally friendly strategies that used a recyclable heterogeneous photosensitizer/acid system with liquid CO 2 as the reaction solvent or applied recyclable aqueous mixtures containing acid and photocatalysts . Recently, Qin and co‐workers developed an efficient photocatalytic radical cascade approach that is based on nitrogen‐centered radicals from aniline‐type sulfonamides and reverses the conventional reactivity between two electron‐donating amine and enamine groups . By applying this photocatalytic radical cascade as a key reaction step, 33 structurally complex monoterpenoid indole alkaloids belonging to four families were successfully synthetized (Fig.…”

“…By applying this photocatalytic radical cascade as a key reaction step, 33 structurally complex monoterpenoid indole alkaloids belonging to four families were successfully synthetized (Fig. ), such as (−)‐vincamine ( 39 , eburnamine‐vincamine family) as a vasodilator, (−)‐yohimbine ( 40 , yohimbine family) as an alpha‐2 adrenoceptor antagonist, (+)‐corynantheol ( 41 , corynanthe family), and (−)‐3‐isoajmalicine ( 42 , heteroyohimbine family) …”

A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine

“…The ingenious landmark synthesis of racemic vallesamidine ( 1 ) by Heathcock and co‐workers was completed in eight steps in 19 % overall yield . Asymmetric variants have taken the form of formal syntheses based on this route or new approaches and vary in length from 15 to 23 steps. Strempeliopine ( 2 ) has been prepared using biomimetic, racemic, and asymmetric multistep syntheses in similar step count.…”

Bioinspired Synthesis of (+)‐Cinchonidine Using Cascade Reactions

“…Retrosynthetically,t he cinchona alkaloids could be accessed by ab iomimetic cascade transformation (i.e., indole to quinoline) of 10 followed by an intramolecular N4-alkylation (Scheme 1B). We envisioned that 10 could be generated by as tereoselective reduction of the C14 À C15 double bond, carbon chain extension at C16, lactam hydrolysis,a nd reduction of tetracyclic intermediate 11.A tt his stage,f acile assembly of the corynanthe-type indole alkaloid skeleton (i.e., 11)w ould be crucial to the success of our proposed synthesis.T ot his end, ac ascade reaction initiated by an itrogen-centered radical would generate the desired tetracycle starting from the known compound 13 [30] and aM ichael acceptor 14.N otably,t his tandem reaction should construct three bonds (N1ÀC2, C3ÀC14, and C15ÀC20) in one pot in ah ighly efficient manner by the mechanism featuring 12.…”

“…As depicted in Scheme 2, the synthesis commenced from the known enamide 16,w hich was easily prepared on ad ecagram scale from the known aldehyde ester 15 [30,31] over five steps.S ubsequently,w ec onducted the radical cascade reaction between the chiral enamide 16 (96 % ee) and isopropyl propionate (17)u tilizing am ethod that was recently developed in our laboratory. [30] To our delight, the anticipated intra-/inter-/intramolecular radical cascade reaction proceeded smoothly with slightly modified reaction conditions,including changing the solvent from THF to DME and using 34 Wr ather than 5W blue LEDs as the light source. [32] In this context, the decagram scale reaction was completed within 10 hours and delivered the tetracyclic product 18 in 83 %y ield with full control of the newly generated stereocenters at C2 and C3, and with d.r.2 0:1a t C20.…”