Total Synthesis of Marinomycins A−C and of Their Monomeric Counterparts Monomarinomycin A and iso-Monomarinomycin A

Abstract

Marinomycins A-C (1-3), and their monomeric analogues monomarinomycin A (m-1) and iso-monomarinomycin A (m-2), were synthesized by a convergent strategy from key building blocks ketophosphonate 5, aldehyde 6, and dienyl bromide carboxylic acid 7. The first attempt to construct marinomycin A [1, convertible to marinomycins B (2) and C (3) by light] by direct Suzuki-type dimerization/cyclization of boronic acid dienyl bromide 4 led to premature ring closure to afford, after global desilylation, monomarinomycin A (m-1) and iso-monomarinomycin A (m-2) in good yield and only small amounts (< or =2%) of the desired product. A subsequent stepwise approach based on Suzuki-type couplings improved considerably the overall yield of marinomycin A (1), and hence of marinomycins B (2) and C (3). Alternative direct dimerization approaches based on the Stille and Heck coupling reactions also led to monomarinomycins A (m-1 and m-2), but failed to deliver useful amounts of marinomycin A (1).

Development of a double allylboration reagent targeting 1,5-syn-(E)-diols: application to the synthesis of the C(23)–C(40) fragment of tetrafibricin

“…4 A key sequence in Nicolaou’s total synthesis of marinomycin A involved a Horner-Wadsworth-Emmons olefination and a syn -reduction of the carbonyl group that provided the 1,5- syn -( E )-diol unit with good diastereoselectivity. 5 In 2010, Friestad published a method for synthesis of the 1,5-( E )-diol unit of tetrafibricin involving the iterative Julia-Kociensky olefination of chiral aldehydes using a chiral α-silyloxy-γ-sulfononitrile. 6 As an alternative, we anticipated that use of a bifunctionalized allylmetal reagent could provide convenient, one-pot access to the 1,5- syn -( E )-diol motif.…”

Benzothiazines in Synthesis. A Formal Total Synthesis of Pseudopteroxazole

“…6 This reagent was then coupled with 2-bromo-3-methoxy-5-methylbenzaldehyde 9 7 to give 10 with high stereoselectivity using Ba(OH)2 as base (Scheme 3). 8…”

Enantioselective Rhodium‐Catalyzed Dimerization of ω‐Allenyl Carboxylic Acids: Straightforward Synthesis of C2‐Symmetric Macrodiolides

“…Aside from unsymmetrical heterogeneous dimers, a group of complex C 2 ‐symmetrical oxacyclic diolides comprise a large number of biologically active compounds (Scheme ). In this group, immunosuppressives,‐ antibiotics,‐ anthelmintics,, herbicides, and fungicides,, as well as active agents against cancer,‐ HIV, and the tropical disease malaria can be found ,. As a consequence these compounds have gained great interest as synthetic targets …”