Preparation, Structure, and Properties of All Possible Cyclic Dimers (Diolides) of 3‐Hydroxybutanoic Acid

Abstract

In connection with the proposed structure of a trans-membrane cellular ion channel consisting of a complex between poly[(R)-3-hydroxy butanoate] (P(3-HB)) and calcium polyphosphate, CaPPi (ca. 150 units each), which is supposed to contain s-cis-bonds or even more highly strained ester conformations, we have prepared and studied the properties of the cyclic dimer of 3-HB, the diolide 1. All possible forms of 1, the rac-, the meso-, and the enantiomerically pure (R,R)-and (S,S)-compounds were prepared, purified, and characterized. The synthesis (Scheme I ) started from dimethyl succinate with the key step being the Baeyer-Villiger oxidation of the rac-and meso-2,5-dimethylcyclohexane-1,d-diones 5. The rat-diolide 1 was resolved by preparative chromatography on a Chiralcel OD column (Fig. 1 ). The crystal structures of rue-1 (Fig. 3 ) and of meso-1 (Fig. 5 ) were determined by X-ray diffraction: the diolides 1 contain s-cis-ester bonds and an ester group with a conformation half way to the transition state of rotation (Fig.2). Strain energies for the diolides 1 of up to 17.8 kcal/mol are suggested. Accordingly, these compounds show reactivities similar to those of carboxylic-acid anhydrides or even acid chlorides. They cannot be chromatographed on silica gel, and they react with primary, secondary, and tertiary alcohols, and with amines to form derivatives of open chain 3-HB 'dimers', hydroxy acids 6, esters 7, and amides 8 (Scheme 2). The rate of acid-catalyzed ring opening of the diolides 1 with alcohols has been measured (Figs.6 and 7). From the results described, we conclude that it is unlikely for strained and reactive ester conformations to occur as part of ion channels through phospholipid bilayers of cells.

Turning On Fluorescence with Thiols – Synthetic and Computational Studies on Diaminoterephthalates and Monitoring the Switch of the Ca2+ Sensor Recoverin

“…Compound 5 [14] and N-Boc-1,2-diaminoethane [15] were prepared according to literature procedures. TLC was performed with Merck SiO 2 F 254 plates on aluminum sheets.…”

“…For this reason, diketone 5 [14] was converted with N-Boc-ethylenediamine [15] by a two-step procedure (Scheme 2). For this reason, diketone 5 [14] was converted with N-Boc-ethylenediamine [15] by a two-step procedure (Scheme 2).…”

Total Synthesis of the Proposed Structure of Ardimerin, and Proposal for its Structural Revision

“…In the 1 H‐NMR spectra of 28 ((D 6 )DMSO, 400 MHz), the geminal coupling between two Bn H‐atoms was observed, suggesting the eight‐membered salicylide core possesses bowl chirality. [7] To observe the dynamic behavior, variable‐temperature 1 H‐NMR experiments were performed. During raising the temperature, the peaks became broadened and coalesced at 355 K, and further heating sharpened the peak.…”

“…[7] Thus, construction of such eight‐membered salicylides is challenging, and reported approaches have been limited, e.g ., condensation of salicylic acid derivative[8] and the Baeyer–Villiger oxidation of cyclohexanedione. [7a] Indeed, Minehan et al . reported the synthesis of the dimethyl‐protected derivative of 1 , although the deprotection failed presumably due to the instability of the eight‐membered salicylide core.…”

Separation of (R)- and (S)-tert-butyl 2-tert-butyl-4-methoxy-2,5-dihydro-1,3-imidazole-1-carboxylate (building block for amino acid synthesis) by preparative high performance liquid chromatography on a polysaccharide stationary phase

“…[3][4][5][6] Since large amounts of the chiral building block 2 were needed and since we had previously applied the method of preparative chromatographic resolutions successfully, [7][8][9][10][11] we decided to resolve the dihydroimidazole rac-2 on a chiral stationary phase.…”