Synthesis of Bioactive Speciosins G and P fromHexagonia speciosa

Abstract

The first total synthesis of speciosins P and G, previously isolated from Hexagonia speciosa, is reported. These compounds have been synthesized by Sonogashira coupling from readily available starting materials. Siccayne was also synthesized from the same starting material in two steps along with a number of other derivatives. The compounds were tested in the wheat coleoptile bioassay. The most active compound was the intermediate 18, followed by 29 and 17. The structural requirements for activity in these compounds are the presence of methoxy groups in the aromatic ring and a formyl or hydroxy group in the side chain.

Enantioselective Total Syntheses of (R)‐ and (S)‐Naphthotectone, and Stereochemical Assignment of the Natural Product

“…Aryl bromides 16 [16] and 18 [17] were also prepared in a straightforward manner. The Sonogashira reaction conditions investigated were similar to those reported previously for the synthesis of speciosins G and P. [7] The coupling of vinyl bromide 15 with diol 2 would lead directly to the naphthoquinone core of the final product. Unfortunately, the desired compound was not detected for any of the conditions we tested.…”

“…Racemic diols 2 [7] and 4 [10] were obtained on a large scale as shown in Scheme 2, and were used to assess the best conditions for the Sonogashira and Heck couplings, respectively. Scheme 2.…”

“…General Procedure for the Sonogashira Coupling: [7] Aryl halide 15, 16, or 18 (2.5 mmol) and n-butylamine (6.4 mL) were put into a flame-dried round-bottomed flask under an argon atmosphere. A mixture of terminal alkyne 2 (1-1.5 equiv.…”

“…[6] The key point in this strategy was the attachment of the side-chain of the naphthoquinone core using a Sonogashira cross-coupling reaction. [7] The α-hydroxylated double bond was obtained with high E selectivity by RedAl [sodium bis(2-methoxyethoxy)aluminum hydride]…”

“…[6] The key point in this strategy was the attachment of the side-chain of the naphthoquinone core using a Sonogashira cross-coupling reaction. [7] The α-hydroxylated double bond was obtained with high E selectivity by RedAl [sodium bis(2-methoxyethoxy)aluminum hydride] [8] reduction of the α-hydroxyacetylenic intermediate produced by the Sonogashira coupling. Final deprotection and oxidation were carried out by the electrochemical reaction mentioned above.…”