Chemical Synthesis and Self-Assembly of a Ladderane Phospholipid

Abstract

Ladderane lipids produced by anammox bacteria constitute some of the most structurally fascinating yet poorly studied molecules among biological membrane lipids. Slow growth of the producing organism and the inherent difficulty of purifying complex lipid mixtures have prohibited isolation of useful amounts of natural ladderane lipids. We have devised a highly selective total synthesis of ladderane lipid tails and a full phosphatidylcholine to enable biophysical studies on chemically homogeneous samples of these molecules. Additionally, we report the first proof of absolute configuration of a natural ladderane.

Selective C−H Halogenation with a Highly Fluorinated Manganese Porphyrin

“…Theh igh efficiencya nd exquisite substrate selectivity of SyrB2 has offered insight and impetus to explore chlorination reactions catalyzed by transition-metal complexes. [15] Zhou and co-workers successfully synthesized ap orphyrinic MOF system by using awater-soluble manganese porphyrin. [10] This method, which employs heteroatom rebound catalysis [11] similar to that of SyrB2 (Scheme 1), has shown remarkable chemo-and regioselectivity.Onthe basis of these initial results,wediscovered that these manganese catalysts also mediated C À Hf luorination with fluoride ion, [12] azidation with aqueous sodium azide, [13] and isocyanation as ar oute to ureas.…”

Photochemical studies on bis-sulfide and -sulfone tethered polyenic derivatives

“…Suitable crystals of 7-OH for a XRD analysis ‡ were obtained which allowed to cross-check the syn-trans-syn relative configuration of cyclobutyl derivatives 7-OH and 7 obtained in all the photochemical experiments (see Schemes 3 and 9). Encouraged by these findings, and also because the intermolecular formation of some ladderanes was reported on using CB [8], 27 we examined the longer systems such as bis-diene and bis-triene ester or acid substrates. In most cases, no conversion was observed and suspected that encapsulation was only partial (only one arm of the substrate) or could also involve two hosts.…”

“…After 24 h, product 7 was present as 58% of the reaction mixture; after extended reaction time (93 h), only 7 was observed. The use of the cucurbit [8]uril (CB [8]) host did not bring any improvement and showed that the medium concentration was a key factor since by diluting, the proportion of product 7 could become major. Nevertheless, encapsulation brought significant improvement compared to our initial conditions (see Scheme 3).…”

“…7 These total syntheses are outstanding tour de force and it is only very recently that the group of Burns came up with a second similarly elegant and efficient total synthesis of natural 3-and 5-ladderanes. 8 Both approaches rely on the [2+2] photochemical cycloaddition which is the obvious methodology to make 4-membered rings 9 but they also involve cyclobutene building blocks which are not straightforward to prepare. 10 …”

Empowering Synthesis of Complex Natural Products

“…In this regard, Burns and co-workersw anted to synthesize an atural mixed ladderane phospholipidc onsisting of [5]-and [3]-ladderane appendages (Scheme8). [36] Recognizing ak ey element of symmetry,B urns leveraged al ate-stage desymmetrization as well as divergent reactivity for each respective ladderane allowing for the use of ac ommoni ntermediate that could be produced on scale.…”