Adriana Lorente

Tetrahydrofuran-containing macrolides: a fascinating gift from the deep sea.

Deep Sea Adriana Lorente,†,‡ Janire Lamariano-Merketegi,†,‡ Fernando Albericio,†,‡,§,# and Mercedes Álvarez*,†,‡,⊥ †Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain ‡CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain School of Chemistry, University of KwaZulu-Natal, 4001-Durban, South Africa Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain

Isolation, structural assignment and total synthesis of Barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. On the basis of preliminary one- and two-dimensional (1)H and (13)C NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. On the basis of the synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.

Phormidolides B and C, Cytotoxic Agents from the Sea: Enantioselective Synthesis of the Macrocyclic Core

New cytotoxic polyketide macrolides named phormidolides B and C were isolated from a marine sponge of the Petrosiidae family collected off the coast of Pemba (Tanzania). The isolation, structure elucidation, and enantioselective synthesis of three diastereomers of the macrocyclic core is described herein. The described synthetic methodology started from 2-deoxy-D-ribose or 2-deoxy-L-ribose and afforded the desired macrocycles with high enantiomeric purity. The key step of the synthesis is the formation of the Z-trisubstituted double bond using a Julia-Kocienski olefination. The versatility of the synthetic methodology may provide access to other enantiopure macrocycles by making changes in the starting materials or chiral inductors.

Selective Formation of a Z-Trisubstituted Double Bond Using a 1-(tert-Butyl)tetrazolyl Sulfone

In our effort to gain further insight into the enantioselective synthesis of the structural core of phormidolides B and C, we have discovered the formation of a Z-trisubstituted double bond. Here, we describe a highly selective process that can be applied to our target following a strategy that is based on Julia-Kocienski olefination. The use of 1-(tert-butyl)tetrazolyl sulfone affords the construction of the Z-trisubstituted alkene with high efficiency and stereoselectivity.

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one, the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

The terminal bromomethoxydiene (BMD) moiety of the polyhydroxylated chain present in phormidolides and oscillariolides has been synthesized for first time. Several strategies for the stereoselective synthesis of the 4-bromo-3-methoxybut-3-en-2-ones are described. Furthermore, a preliminary study to successfully introduce the BMD within the polyol chain and the fatty acid allowed us to corroborate the end structure of the polyol.

Enantioselective Synthesis of the Polyhydroxylated Chain of Oscillariolide and Phormidolides A–C

The first enantioselective synthesis of the polyhydroxylated chain common to marine natural products oscillariolide and phormidolides A-C is described herein. This chain represents a synthetic challenge that needs to be solved before the total synthesis of this family of natural products can be approached. It contains seven stereocenters, six of them having a syn-hydroxylated functionality, and a tricky terminal (E)-bromomethoxydiene (BMD). The described effective enantioselective strategy affords the polyketide chain and represents an important breakthrough to complete the total synthesis of these marine compounds.

Stereoselective Allylstannane Addition for a Convergent Synthesis of a Complex Molecule.

A convergent methodology with 13 lineal steps for the synthesis of phormidolides B and C macrocyclic core is described. Stereoselective formation of the tetrahydrofuran (THF) core was achieved using a stereocontrolled allylation reaction. The key step of the synthesis is a (Z)-1,5-anti stereoselective allylstannane addition where a new stereocenter and a trisubstituted double bond are formed simultaneously. Finally, Shiina macrolactonization conditions improved the yield of the final cyclization.