Naturally Occurring Allenes

Allenes are compounds with adjacent carbon-carbon double bonds. Many allenes are chiral, even though they don t contain chirality centers. Mycomycin, for example, a naturally occurring antibiotic isolated from the bacterium Nocardia acidophilus, is chiral and has = -130. Explain why mycomycin is chiral. Making a molecular model should be helpful. 

Isomerisation Reactions of Naturally Occurring Allenes. J. Chem. Soc. [London] 1956, 3767. 

Scheme 18.10 Naturally occurring allenic amino acid (26) and allenic hydrocarbons (27).

About 20 years ago, Bohlmann and co-workers examined South American plants of the widespread Vemonia species and found the first and (until now) only naturally occurring endocydic allenes (Scheme 18.32) [97]. These are the bicyclic sesquiterpene lactones 100-102 bearing a 10-membered ring [98], in which the E-double bond of the larger ring can also be present in its oxidized form (101, 102). As in other cases, these fasdnating natural products have not been synthesized until now. 

Pharmacologically active allenic steroids have already been examined intensively for about 30 years [5], Thus, the only naturally occurring allenic steroid 107 had been synthesized 3 years before its isolation from Callyspongia diffusa and it had been identified as an inhibitor of the sterol biosynthesis of the silkworm Bombyx mori (Scheme 18.34) [86d], At this early stage, allenic 3-oxo-5,10-secosteroids of type 108 were also used for the irreversible inhibition of ketosteroid isomerases in bacteria, assuming that their activity is probably caused by Michael addition of a nucleophilic amino acid side chain of the enzyme at the 5-position of the steroid [103, 104]. Since this activity is also observed in the corresponding /3,y-acetylenic ketones, it can be rationalized that the latter are converted in vivo into the allenic steroids 108 by enzymatic isomerization [104, 105],... 

Interestingly this correction was not included in the well-known monograph by Schuster and Coppola [lc] there, pyrothro-lone is mentioned on p. 1 as the first naturally occurring allene. 

Hiemstra and co-workers reported the first example of an iodine-promoted allenyl N-acyliminium ion cyclization for the total synthesis of (+)-gelsedine, the enantiomer of the naturally occurring (-)-gelsedine [72], Compound 341 was prepared from (S)-malic acid. When 341 was dissolved in formic acid with a large excess of Nal and heated at 85 °C for 18 h, 343 was found to be the major product isolated in 42% yield. The latter was then successfully converted to (+)-gelsedine in a multi-step manner. Other routes without the allene moiety failed to provide the desired stereoisomer. The successful one-step transformation of 341 to 343 was key to the success of this synthesis. 

Stoichiometric enantioselective addition of lithium aluminum hydride, modified with ( — )-men-thol or sugar derivatives as chiral auxiliaries to enynols provides an entry to /Thydroxyallenes of low enantiomeric purity117 119. This method has mainly been used to establish absolute configurations of naturally occurring allenes, e.g., (—)-marasin119, and has not been optimized. 

Chiral allenes. A key step in a recent synthesis of the optically active pheromone of the male boll weevil (3) used the orthocstcr Claisen rearrangement for transfer of the chirality of the acetylenic alcohol 1 to the allene 2. The final product (3) shows a higher optical rotation than the naturally occurring material, which may... 

Various applications of the method have been reported324,325,325 1 and include the efficient formation of the functionalized furan 388, a precursor of the agylcon 389 of the naturally occurring antibiotic eleutherobin, from the allenic ketone 387 (Scheme 113).328... 

The synthetic route described here has been used for various skipped diynes and related 1,3-diynes, among which are precursors or analogs of naturally occurring polyynes.2 The cuprous chloride-promoted coupling reaction in tetrahydro-furan provides the best and often the sole route to the 1,4-diynes.2 From these it is simple to proceed to the 1,3-diyne, possibly with a stop on the way at the isomeric allene.2-6 Because all of these compounds appear to be sensitive, e.g., to heat and oxygen, the relatively mild conditions of their syntheses are noteworthy. 

The present route to conjugated diynes is the method of choice if the corresponding skipped diyne or allene is available.2-6 With naturally occurring polyynes this is often the case. Depending on the 1,4-diyne, the base-catalyzed isomerization may be successfully stopped (by acidification) to yield the intermediate allenylacetylene. Since the isolation of the allene may or may not be desired, it seems prudent to monitor the progress of isomerization of new 1,4-diynes, e.g., by n.m.r., and establish the approximate lifetimes of transient species. In this way some allenes as well as conjugated diynes may be obtained.6... 

Jensen, W.I., Allen, J.P. (1981). Naturally occurring and experimentally induced castor bean (Ricinus communis) poisoning in ducks. Avian Dis. 25 184-94. 

Arredondo, V.M., Tian, S., McDonald, EE. et al. (1999) Organolanthanide-catalyzed hydroamina-tion/cyclization. Efficient allene-based transformations for the syntheses of naturally occurring alkaloids. Journal of the American Chemical Society, 121, 3633. 

A study of the influence of silica gel surfaces on the photochemical addition of allene to a series of cyclic enones has been carried out. Using this technique cycloaddition occurs to the more hindered face of the enone. A typical example of allene addition, where addition takes place to the less hindered face, is reported by Piers et al. in the photoaddition to the enone (65) which affords the four isomeric products (66) in ratios of 40 51 6 3. The two major products (66a) and (66b) were used as starting materials for total syntheses of naturally occurring compounds of the stemodane type. ... 

Allen reported in 1977 that naturally occurring 3-oxo (or 3-keto) macrolides such as pikromycin (81a) and narbomycin (81b) (Fig. 19) do not induce mac-rolide resistance in S. aureus, and they retained sufficient antibacterial activity [108]. On the other hand, derivatives of 3-decladinosyl-3-oxo-6-0-methyl EM (82) (Fig. 20) have been recently synthesized and designated as ketolides [109]. They generally exhibit significant activity against EM-resistant Gram-positive pathogens, and the features of their activity are fairly different from those of EM derivatives that bear cladinose at the C-3 position. 

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