A Sequential Two‐Component Etherification/Oxa‐Conjugate Addition Reaction: Asymmetric Synthesis of (+)‐Leucascandrolide A Macrolactone

Evans, P. Andrew; Andrews, William J.

doi:10.1002/ange.200801357

Cited by 6 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We consequently synthesized ethyl (10R)-benzyloxy-(8R)-benzoyloxy-(3R)-tert-butyldimethylsilyloxy-undec-5E-enoate by Grubbs' ruthenium-catalyzed olefin cross-metathesis of 3 and 6, which were obtained from the chiral synthons 1 and 4 as previously described (22,23) (Fig. 2E).…”

Section: Resultsmentioning

confidence: 99%

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Choe

Chuman

Reuß

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples of a female-or hermaphrodite-specific sex attractant have been identified to date. In this study, we investigated the pheromone system of the gonochoristic sour paste nematode Panagrellus redivivus, which produces sex-specific attractants of the opposite sex. Activity-guided fractionation of the P. redivivus exometabolome revealed that males are strongly attracted to ascr#1 (also known as daumone), an ascaroside previously identified from Caenorhabditis elegans hermaphrodites. Female P. redivivus are repelled by high concentrations of ascr#1 but are specifically attracted to a previously unknown ascaroside that we named dhas#18, a dihydroxy derivative of the known ascr#18 and an ascaroside that features extensive functionalization of the lipid-derived side chain. Targeted profiling of the P. redivivus exometabolome revealed several additional ascarosides that did not induce strong chemotaxis. We show that P. redivivus females, but not males, produce the male-attracting ascr#1, whereas males, but not females, produce the female-attracting dhas#18. These results show that ascaroside biosynthesis in P. redivivus is highly sex-specific. Furthermore, the extensive side chain functionalization in dhas#18, which is reminiscent of polyketide-derived natural products, indicates unanticipated biosynthetic capabilities in nematodes.hemical communication plays an important role in the biology of many free-living and parasitic nematodes (1). Recent studies have shown that a family of small-molecule signals, the ascarosides, control sexual attraction (2-5), aggregation (6, 7), olfactory plasticity (8), dauer formation (9-12), and dispersal (13) in the model organism Caenorhabditis elegans. Ascarosides ( Fig. 1) are glycolipids derived from the dideoxysugar ascarylose, which in some cases, bear additional moieties, such as para-aminobenzoic acid and indole carboxy-or p-hydroxybenzoyl groups. The diversity of behavioral effects modulated by ascarosides in C. elegans is paralleled by complexity of ascaroside structures. Targeted metabolomicsbased analysis of wild-type C. elegans exudates (i.e., the exometabolome) resulted in the detection of over 50 ascaroside components, many of which have no known function (14). Using LC-MS analysis, we have previously shown that ascaroside signaling is not restricted to C. elegans and is widely conserved among nematodes (15). Many free-living and parasitic nematode species were shown to release ascarosides. However, the species-specific functions of the identified ascarosides remain largely unknown. Moreover, this targeted analysis focused exclusively on ascarosides previously identified from C. elegans, and it seems likely that other nematode species produce additional ascarosides not present in C. elegans.In this study, we used activity-guided fractionation to isolate both male-an...

show abstract

Section: Resultsmentioning

confidence: 99%

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Choe

Chuman

Reuß

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Synthesis plan: We initially targeted the proposed structure 1 of neopeltolide because the correct structure 2 had not yet been elucidated at the outset of our work. According to the literature precedents on the synthesis of the structurally related marine macrolide leucascandrolide A, [14,15] we planned to incorporate the oxazole-containing side chain at the final step of the total synthesis through Mitsunobu esterification [16] of alcohol 3 and the known acid 4 [15] (Scheme 1). We envisaged the 14-membered macrolactone core structure of 3 to be derived from tetrahydropyran 5 via Yamaguchi lactonization.…”

Section: Resultsmentioning

confidence: 99%

“…Hydrogenolysis of the benzyloxymethyl (BOM) ether of 28 delivered alcohol 3 in 100 % yield. Finally, Mitsunobu esterification of 3 with the known acid 4 [15] under standard conditions (diisopropyl azodicarboxylate (DIAD), Ph 3 P, benzene, room temperature) furnished the proposed structure 1 of neopeltolide in 86 % yield. The spectroscopic properties of 1 did not match those of the natural product (that is, the correct structure 2) but were in close agreement with the data for 1 reported by Panek and co-workers [3] and Scheidt and co-workers.…”

Section: Synthesis Of Acyclic Enol Phosphatementioning

confidence: 99%

Total Synthesis and Biological Evaluation of (+)‐Neopeltolide and Its Analogues

Fuwa

Saito

Naito

et al. 2009

Chemistry A European J

View full text Add to dashboard Cite

The stereocontrolled total synthesis of the originally proposed (1) and correct (2) structures of (+)-neopeltolide, a novel marine macrolide natural product with highly potent antiproliferative activity against several cancer cell lines as well as potent antifungal activity, has been achieved by exploiting a newly developed Suzuki-Miyaura coupling/ring-closing metathesis strategy. Alkylborate 44, which was generated in situ from iodide 34, was coupled with enol phosphate 8 by a Suzuki-Miyaura coupling. Ring-closing metathesis of the derived diene 45 followed by stereoselective hydrogenation afforded tetrahydropyran 47 as a single stereoisomer in high overall yield from 34. Our convergent strategy enabled us to construct the 14-membered macrolactone core structure of 2 in a rapid and efficient manner. Total synthesis and biological evaluation of synthetic intermediates and designed synthetic analogues, performed to establish the structure-activity relationships of 2, led to the discovery of a structurally simple yet potent cytotoxic analogue, 9-demethylneopeltolide (54).

show abstract

Rhodium‐Catalyzed Cyclization of Terminal and Internal Allenols: An Atom Economic and Highly Stereoselective Access Towards Tetrahydropyrans

Breit

Schmidt

2020

Angewandte Chemie

View full text Add to dashboard Cite

A comprehensive study of a diastereoselective Rh‐catalyzed cyclization of terminal and internal allenols is reported. The methodology allows the atom economic and highly syn‐selective access to synthetically important 2,4‐disubstituted and 2,4,6‐trisubstituted tetrahydropyrans (THP). Furthermore, its utility and versatility are demonstrated by a great functional‐group compatibility and the enantioselective total synthesis of (−)‐centrolobine.

show abstract

A Sequential Two‐Component Etherification/Oxa‐Conjugate Addition Reaction: Asymmetric Synthesis of (+)‐Leucascandrolide A Macrolactone

Abstract: Sanfte Synthese: Die konvergente asymmetrische Synthese des Macrolactons (+)‐Leucascandrolid A (siehe Struktur) mit einer längsten linearen Sequenz von 14 Stufen ergibt das Produkt in 20 % Gesamtausbeute. Die 1,5‐Tetrahydropyran‐Struktur wird dabei in nur einer Stufe aufgebaut.

Cited by 6 publications

References 40 publications

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Total Synthesis and Biological Evaluation of (+)‐Neopeltolide and Its Analogues

Rhodium‐Catalyzed Cyclization of Terminal and Internal Allenols: An Atom Economic and Highly Stereoselective Access Towards Tetrahydropyrans

Contact Info

Product

Resources

About