Superacid‐Catalyzed Cyclization of Methyl (6Z)‐Geranylfarnesoates

Abstract

Methyl (2Z,6Z,10E,14E)-(3) and methyl (2E,6Z,10E,14E)-geranylfarnesoate (4) were prepared, and then individually cyclized in the presence of the superacid FSO 3 H. In the case of substrate 3, the scalaranic ester 9 (26%) and the cheilanthanic ester 10 (39%) were isolated. Under the same conditions, substrate 4 afforded a mixture of the corresponding stereoisomers 11 (25%) and 12 (63%). The observed product selectivity supports that the internal, (6Z)-configured C¼C bond in these and other biologically relevant substrates plays an essential role in the cyclization process.Introduction. -Prenols represent a large class of natural, linear isoprenoids that occur abundantly in plant kingdom. Their diversity is due to the (E/Z)-configuration of the C¼C bonds and their chain length, which may vary from two (in monoterpenols) to several thousand (in natural rubber) isoprene units [1]. Terpenols with short chain lengths (up to five isoprene units) having all their C¼C bonds in (E)-configuration are regarded as biogenetic precursors of the corresponding cyclic isoprenoids. Based on this notion, many biomimetic syntheses of cyclic terpenoids have been elaborated, which turned out to serve not only as demonstrations of the biogenetic origin of cyclic isoprenoids, but also as very efficient synthetic tool for their in vitro preparation. Superacid-catalyzed cyclization of regular-structured, short-chain terpenoids is one of the most-successful biomimetic procedures to establish a link between the cyclic compounds and their aliphatic precursors [2].Biomimetic cyclization of long-chain polyprenols has also been investigated, and successful attempts of both enzymatic [3] and superacidic [4] cyclization have been reported; but only prenols with (all-E)-configuration have been used as substrates. On the other hand, it is known that most of the natural long-chain polyprenols possess the so-called di-trans-poly-cis or tri-trans-poly-cis configuration 1 ). To the best of our knowledge, none of these compounds have been used as substrates for biomimetic cyclizations.We have shown in recent papers [5] [6] that the presence of an internal (13Z)-configured C¼C bond in the bicyclic, stereoisomeric compounds methyl (13Z,17Z)-(1) and methyl (13Z,17E)-bicyclogeranylfarnesoate (2) influences the selectivity of the

Reductive Heck Reaction: An Emerging Alternative in Natural Product Synthesis

“…Among scalarane sesterterpenoids, sesterstatins 4, 5 and scalarafuran are the most familiar and known for their potent cytotoxic and inhibiting activities of HIV‐1 integrase . In an addition to previous aproaches Deng group reported synthesis of sesterstatins 4 and 5 in several steps using reductive Heck cyclization as a key synthetic step for constructing target compounds (Scheme ) .…”

Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products

“…The absence of stronger nucleophiles in these alkylation reactions resulted in the isolation of formyl cytosine. Other readily available N-heterocyclic compounds were also alkylated, including the pyrimidines, uracil (51), thymine (52), and cytosine (53). Alkylation of 51, and 52 yielded only N-1 monoalkylated derivatives (54)(55)(56)(57)(58)(59) whereas 53 only produced N-1,N-3 dialkylated products (61, 63) (Scheme 6).…”

“…Methyl iodide was run through a plug of activated alumina prior to use. 2-Mercapto-3-methylhypoxanthine [50], the relevant terpenoid bromides [51][52][53], and terpenoid amines [41] were synthesized according to literature. The C-2 alkene E/Z ratio of the terpenoid bromides was determined from integrated peak areas detected by 1 H NMR spectroscopy.…”

Combining the Power of TiIII‐Mediated Processes for Easy Access to Hydroxylated Polycyclic Terpenoids: Synthesis of Sesterstatin 1 and C–D Rings of Aspergilloxide

“…With the exception of the total synthesis of scalarenedial, [21] other related scalaranes have been only prepared in a semisynthetic manner from natural sources, such as bicyclic terpenes sclareol or manool. [22] Our very short synthesis of 1 from 47 is depicted in Scheme 5.…”