Synthetic Studies Towards the Core Tricyclic Ring System of Pradimicin A

Abstract

Pradimicins are structurally intriguing natural products that possess potent biological activity as antifungal and antiviral agents through a unique mode of action as carbohydrate binding agents. A preliminary synthetic approach towards pradimicin A has focused on a model study of the core tricyclic ring system. The route features an alkoxyallylboration/cycloisomerization/Diels–Alder cycloaddition sequence as the key steps. The alkoxyallylboration was critical for differentiating the hydroxy groups in the central cyclohexadienediol unit of pradimycins, which will ensure a regiocontrolled glycosylation. For the cycloisomerization reaction, various substrates and conditions were tested for a ring‐closing enyne metathesis reaction. With enyne substrate 23, dimerization‐prone bicyclic diene 24 was isolated as the major product under the conditions of both ruthenium‐catalyzed metathesis and palladium‐catalyzed cycloisomerization. In the end, the optimal route found for the synthesis of the model functionalized tricyclic ring system 31 features a one‐pot sequential palladium‐catalyzed cycloisomerization, Diels–Alder reaction, and oxidative aromatization.

Sequencing palladium-catalyzed cycloisomerization cascades in a synthesis of the gelsemine core

“…[5][6][7][8][9][10][11][12] When substrates feature multiple unsaturated bonds, elegant cascade processes have been developed whereby intermediate alkyl-or alkenylpalladium species undergo multiple C-C bond forming events in a single step; 13 one pioneering example from the Trost group is shown in Scheme 1a (1 / 2). 14 Pd-catalyzed cycloisomerizations have also been widely used in total synthesis, 1,[15][16][17][18][19][20][21][22] however applications of cascade cycloisomerizations are rare in this context. Sequential cycloisomerizations have been reported, such as an elegant approach to dendrobine described by the Chen group in which palladium-and rhodium-catalyzed cycloisomerizations were implemented in consecutive steps to construct the bicyclic pyrrolidine 3 from dienyne 4.…”

Asymmetric Total Synthesis of PD-116740

“…Shi and co-workers developed a Pd-catalyzed atroposelective C–H olefination to construct the axially chiral biaryls, which was used in the total synthesis of TAN-1085 ( 4 ) (Scheme B) . Recently, we developed a new strategy involving an asymmetric dihydroxylation and a Cu-mediated oxidative phenol coupling reaction to build the trans -dihydrophenanthrenediol fragment which was used in the total synthesis of FD-594 (Scheme C) . As a further application of this strategy, we reinvestigated the Cu-promoted oxidative cyclization and achieved the asymmetric total synthesis of (+)-PD-116740.…”

Stereoselective Synthesis of 1,4-Diols by a Tandem Allylboration–Allenylboration Sequence

“…The reaction of 1 with (di)­aldehydes ( 2 ) may be initiated by allylboration of the carbonyl group . This allylation method has been widely employed for the diastereoselective synthesis of homoallylic alcohols. , Allylboration of carbonyl compounds with 1 is interesting both synthetically and mechanistically. The reaction provides allenylboronate 3 with two types of stereogenic units.…”