Synthetic Studies Toward (–)-versicolamide B And Construction Of Indole Alkaloid Skeleton By Photocatalytic Radical Cascade

This thesis consists of two parts:(1)synthetic studies towards the total synthesis of(–)-versicolamide B and(–)-depyranoversicolamide B;(2)efficient construction of corynanthe indole alkaloid skeleton by photocatalytic free radical cascade reaction.(1)(–)-Vericolamide B was isolated from marine fungus Aspergillus sp.MF 297-2 by Williams group,which containing two isopentenyl groups.One isopentenyl which connected to indole C3 position,forms the unique bicyclo[2.2.2]diazaoctane structure center(E,F double ring)through intramolecular Diels–Alder reaction.Another isopentenyl is linked to indole C6 and C7 position,forming dimethyl pyrano ring(A ring).Intramolecular Diels-Alder strategy is the most concise and efficient method to construct bicyclo[2.2.2]diazaoctane skeleton.In this paper,starting from easily prepared(R)-C3-isoprenylated pyrroloindoline 219,the asymmetric total synthesis of(–)-depyranoversicolamide B(30)was successfully completed in 15 steps with 6.7% overall yield.The whole synthetic route is succinct and efficient.The key reactions in the route are described as follows:(1)pyrrolo-indoline intermediate 235 was efficiently transformed to C3-isoprene indoline compound 236 under the conditions of titanium tetrachloride and sodium cyanoborohydride.(2)C3-isoprene indoline diketopiperazine 271 can generate the anti-addition product 273 stereoselectively via intramolecular Diels-Alder reaction.(–)-Depyranoversicolamide B(30)possesses the same bicyclo [2.2.2]diazaoctane skeleton compared to(–)-versicolamide B(1),only lacking the pyrano ring unit.(2)The photocatalytic free radical cascade reaction which is applied to construct indole and indoline skeletons,has the advantages of succinctness,efficiency,economical,mild and green.A new method of generating nitrogen free radicals directly from amide functional groups without the derivatization of nitrogen atom in mild conditions is developed.The radical cascade can controllably introduce complexity and functionality into products with excellent chemo-,regio-,and diastereoselectivity.The reaction conditions are mild,and the reaction can be scaled up to 10 grams.By using this photocatalytic intramolecular/intermolecular/intramolecular free radical cascade as a key reaction,135 i reacted with 130 g delivered the corynanthe-type skeleton product efficiently.Natural products(-)-mayumbine(173)and(+)-ajmalicine(175)were synthesized successfully,and this realized the efficient cluster synthesis of monoterpene indole alkaloids.