Total Synthesis of Bryostatin 8 Using an Organosilane‐Based Strategy

Abstract

Convergent total synthesis of bryostatin 8 has been accomplished by an organosilane-based strategy. The C ring is constructed stereoselectively through a geminal bis(silane)-based [1,5]-Brook rearrangement, and the B ring through geminal bis(silane)-based Prins cyclization, thus efficiently joining the northern and southern parts of the molecule.

Unlocking the Drug Potential of the Bryostatin Family: Recent Advances in Product Synthesis and Biomedical Applications

“…In 2018, bryostatin 8 was successfully synthesized by Song and co-workersi n4 8s teps with an LLS of 29 steps. [49] The team used an approach similar to Wender's convergent synthetic strategy to reduce linear steps and improve yield. Twom ain fragments (i.e.,t he Ba nd Cr ing) were constructed by using geminalb is(silane) chemistry (Scheme 5a nd 6), where the B ring was obtained through Prins cyclization and the Cr ing through [1,5]-Brook rearrangement (Scheme 7).…”

“…[56] Then Wender et al designedafirst analoguei n1 998 (Figure 4), which separated the A-/B-ring fragments and the C-ring fragment.F ollowing studies have indicatedt hat the functionality of the C-ring fragment contacts PKC and thus influences affinity,w hich namedt he recognition domain. [49,57] TheA -a nd B-ring fragments are proposed to enhance affinity by controlling the alignment of the C-ring binding elements and to influence functionb ya ffecting PKC translocation and/orm embrane insertion( which namedt he spacer domain). [53k, 58] The salicylate subunit replaced the A-and B-ring fragments of bryo 1 and acted as an orthern parto ft he bryostatin molecule, that is, as a" spacer domain".…”

“…In 2018, bryostatin 8 was successfully synthesized by Song and co‐workers in 48 steps with an LLS of 29 steps . The team used an approach similar to Wender's convergent synthetic strategy to reduce linear steps and improve yield.…”

“…designed a first analogue in 1998 (Figure ), which separated the A‐/B‐ring fragments and the C‐ring fragment. Following studies have indicated that the functionality of the C‐ring fragment contacts PKC and thus influences affinity, which named the recognition domain . The A‐ and B‐ring fragments are proposed to enhance affinity by controlling the alignment of the C‐ring binding elements and to influence function by affecting PKC translocation and/or membrane insertion (which named the spacer domain) .…”

Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle 23 Has Negligible Impact on Its Biological Profile and Potency

“…The first total synthesis of bryostatin 1 was reported by Keck and co‐workers in 2011 . Other elegant total syntheses in this area were also published, including bryostatin 16 by Trost, bryostatin 7 by Krische, bryostatin 9 by Wender, and bryostatin 8 by Song …”