Synthesis of the Rosette-Inducing Factor RIF-1 and Analogs

Abstract

Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development.

Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates

“…Additional activity-guided fractionation by HPLC allowed us to isolate pure samples of RIF-1 (35,43) and of the 605-Da sulfonolipid. Purified RIF-1 induced maximal (∼1.5%) rosette development at femtomolar to nanomolar concentrations ( Fig.…”

Choanoflagellate models — Monosiga brevicollis and Salpingoeca rosetta

“…Analysis of the lipid extract of A. machipongonensis revealed that a specific molecule, a sulfonolipid called RIF-1 (rosette inducing factor), is responsible for the induction of colony formation (Figure 2f) [38 ]. RIF-1 synthesized in vitro also induces colony formation [39], and additional molecules, synergizing with RIF-1 in its colony inducing effect have been identified [40]. The sequencing of the genome and transcriptome of S. rosetta has further contributed to our understanding of the putative genome composition of animal ancestors [10].…”

Progress in the trans-Reduction and trans-Hydrometalation of Internal Alkynes. Applications to Natural Product Synthesis

“…81 Key to success was the conversion of a propargylic alkyne group to a 1,3-diol, which was accomplished by trans-hydrosilylation of the propargylic alcohol 92 to give alkenyl silane 93 with high regiocontrol (β:α = 95:5). A subsequent TamaoFleming oxidation 33,34 and stereoselective reduction of the resulting ketone afforded the desired 1,3-syn diol.…”