Total Synthesis of Enantiopure Pyrrhoxanthin: Alternative Methods for the Stereoselective Preparation of 4‐Alkylidenebutenolides

Abstract

A new stereocontrolled total synthesis of the configurationally labile C37 -norcarotenoid pyrrhoxanthin in enantiopure form has been completed. A highly stereoselective Horner-Wadsworth-Emmons (HWE) condensation of a C17-allylphosphonate and a C20-aldehyde was used as the last conjunctive step. Both a Sonogashira reaction to form the C17-phosphonate and the final HWE condensation proved to be compatible with the sensitive C7-C10 enyne E configuration. Regioselective (5-exo-dig) silver-promoted lactonization reactions of three alternative pent-2-en-4-ynoic acid precursors with increased complexity, including a fully functionalized C20-fragment, were explored for the preparation of the γ-alkylidenebutenolide fragment. This survey extends the existing methodologies for the preparation of oxygen-containing carotenoids (xanthophylls) and streamlines the synthesis of additional members of the C37-norcarotenoid butenolide family of natural products.

Complex Polymer Topologies Built from Tailored Multifunctional Cyclic Polymers

“…The crude product was isolated as yellow oil and used without further purification (yield=57.02%). The 1 H and 13 C NMRs are given in Figure S1 in the Supporting Information, and were in agreement with literature …”

“…The 1 H and 13 C NMRs are given in Figure S1 in the Supporting Information, and were in agreement with literature. 46 Synthesis of 3-Bromoprop-1-ynyl-3-(1,1,1-triisopropyl)silane (3). A solution of 3-(1,1,1-triisopropylsilyl)-2-propyn-1-ol (2) (6.0 g, 28.25 × 10 −3 mol) and pyridine (13.7 × 10 −3 mL, 1.69 × 10 −3 mol) in anhydrous diethyl ether (100 mL) was cooled to 0 °C in an ice bath.…”

Sonogashira coupling in natural product synthesis

“…Natural products containing conjugated enynes or enediynes have attracted considerable attention from organic chemists and biologists because of their sensitive structural features and their potential as bioactive compounds and as starting compounds in chemical biology studies. [3][4][5][6][7] The total synthesis of these natural products is challenging mostly because of the difficulty in efficiently constructing the sensitive motif containing the conjugated enynes and enediynes. Inter-or intramolecular Sonogashira reactions to construct the sp-sp 2 bond have proven useful for achieving this step.…”

“…The Sonogashira reaction is also used as a key coupling step in the convergent syntheses of pyrrhoxanthin (2) 4 and callipeltoside A (28), 3 both of which contain conjugated enynes (Scheme 7). Coupling a trisubstituted dienyl iodide 22 with terminal alkyne 23 in the presence of Pd(PPh 3 ) 4 and CuI in n BuNH 2 in benzene gave the desired product 24 in 56% yield.…”

“…2 These reactions dramatically improve the efficiency of organic syntheses, such as those involving the formation of sp-sp 2 bonds. These bonds occur in arylalkynes, conjugated enynes and enediynes, synthons that occur in such natural products as phorbaside A (1), 3 pyrrhoxanthin (2), 4 dynemicin A (3), 5 kedarcidin chromophore (4) 6 and calicheamicin γ 1 (5) 7 (Fig. 1).…”