Alkaloids cyclo

Some alkaloids were found in nature to be derivatives of the celacinnine alkaloids, having an additional bond between the N1 substituent and the spermidine moiety. It seems that the precursors of the four alkaloids cyclo-celabenzine (134), isocyclocelabenzine (135), hydroxyisocyclocelabenzine (136), and pleurostyline (137) (Scheme 25) contain enamine systems that are able to cyclize. The structure elucidation of 134,135,136, and 137 was based on extensive spectroscopic analysis, mainly H- and 13C-NMR spectra of the alkaloids, their acetyl, and, in case of 137, their dihydro derivatives... 

S. pseudocapsicum Low incorporations were found into each alkaloid. Cyclo-artanol was the better precursor of the two. In the case of tomatidine (185) the radioactivity was shown to be confined to ring f, indicating intact incorporation of the C27 precursor. Similar low incorporations had been recorded with cholesterol into tomatidine/ although other workers had found good incorporation into tomatidine and solanidine. ... 

The phenanthroindolizidine alkaloid (-)-antofine (95) exhibits high cytotoxicity to drug-sensitive and multidrug-resistant cancer cells by arresting the G2/M phase of the cell cycle. In the first asymmetric total synthesis of (-)-95, the late-stage construction of pyrrolidine 94 for the final Pictet-Spengler cyclo-methylenation to 95 was performed by RCM and subsequent hydrogenation (Scheme 18) [67]. 

A molybdenum-mediated oxidative coupling of aniline 1 with cyclohexene 2a provides carbazole 3. Alternatively, the same overall transformation of aniline 1 to carbazole 3 is achieved by iron-mediated oxidative coupling with cyclo-hexa-1,3-diene 2b or by palladium-catalyzed oxidative coupling with arenes 2c. The use of appropriately substituted anilines and unsaturated six-membered hydrocarbons opens up the way to highly convergent organometallic syntheses of carbazole alkaloids. 

During the synthesis of 436, Muraoka and colleagues produced the diazobi-cyclo[4.3.1]decane 435 via the classical ring expansion (equation 184). Huisgen-White rearrangement of the cyclic lactam leads to 436, a key synthetic intermediate for piperidine alkaloids. 

Numerous Amaryllidaceae alkaloids include phenanthridine skeletons, one of whose constructive methods constitutes an IEDA strategy. In some cases, the functionality on the dienophile influences the stereochemistry of cyclo addition reactions under high-pressure conditions. For example, the reactions of ( )-buta-l,3-dienyl acetate (6) and the quinolin-2(lH)-ones 7 gave rise to different configurations in the products 8 and 9, depending on the functional groups at the 4-position of 7 (Scheme 3). These results reflect... 

Two new alkaloids, cyclobuxophylline-O (Id) and buxithienine-M (3), have been isolated from leaves of Buxus sempervirens var. rotundifolia. Also isolated were the known alkaloids buxamine-E, buxaminol-B, buxpiine-K, buxtauine-M, cyclo-bullatine-A, cyclobuxine-D, cycloprotobuxine-C, and cyclovirobuxine-D (4),... 

Interestingly, a series of similar cyclo(Pro,Pro) diketopiperazines, named verpa-camides (e.g. 48), have been isolated from the marine sponge Axindla vaceleti [76]. It was proposed that these molecules could be the biogenehc precursors of the C11N5 skeleton, common to all the alkaloids of this class, through an intramolecular oxidative rearrangement, via a dioxetanone intermediate. 

As in the case of chromatography, a chiral selector is also required in CE for enantiomeric resolution. Generally, suitable chiral compounds are used in the background electrolyte (BGE) as additives and hence are called chiral selectors or chiral BGE additives. There are only a few publications available that deal with the chiral resolution on a capillary coated with the chiral selector in CE. The analysis of the chiral pollutants discussed in this chapter is restricted only to using chiral selectors in the BGE. The most commonly used chiral BGE additives are cyclo-dextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and alkaloids.A list of these chiral BGE additives is presented in Table 1. 

The above mentioned isomerization of CCCLI to CCCLII constitutes a route from the 9/3,19-cyclosteroids to a new skeletal type which is characteristic of a small group of Buxus alkaloids and will be dealt with in the subsequent text. Another reaction applied to an analogous structural type and leading to cleavage of the cyclopropane ring was reported by Kupchan and Abushanab 219) who had subjected 9, 19-cyclo-5a-pregnane-3,l 1,20-trione-3,2()-diethylene ketal to Wolff-Kishner reduction and obtained a mixture of 10-epimeric ketals CCCLX and CCCLXI. 

No attempt as yet has been made to study the biogenesis of Buxus alkaloids. Indirect evidence gave rise to the presumption that in the biogenetic scheme lanosterol is followed by cycloartenol (or similar triterpene type). Goutarel (205) tentatively proposed a possible pathway via lanosterol, cycloartenol, 9j8,19-cyclo-4,4, 14a-trimethyI-5a-pregnan-3(8 - ol - 20 - one, 9, 19 - cyclo - 4,4, 14a - trimethyl - 5a - pregnan - 3,20 - dione, mono-, and diaminosteroids. 

Buxus malayana, - Buxus rolfei, Buxus sempervirens, and Buxus koreana. With few exceptions, these alkaloids have an unusual skeleton containing a cyclopropane ring and are derived from the, 1406-trimethyl-9P, 19-cyclo-5c --pregnane systan. 

The Denmark laboratory has developed an elegant tandem [4 + 2]/[3 + 2]-cyclo-addition strategy for the synthesis of a variety of alkaloid natural products (96CR137). Nitroethylene (166) readily undergoes a Lewis acid promoted cycloaddition with vinyl ethers that contain a chiral auxiliary group to give nitronates 168... 

In general, alkaloids of type I include the prefix cyclo in their names ... 

Since several newly-discovered alkaloids contain the 9/S,19-cyclo-ll-oxo conjugated system, it has been proposed to use the prefix cycloxo in naming them. Further, since many alkaloids contain the amide function, it has become customary to indicate this function in their names. Thus baleabuxine and the baleabuxidines are named as follows ... 

The origin of the steroidal alkaloids of the Apocynaceae and some of the Buxaceae (Sarcococca and Pachysandra) appears to be linked with the biogenesis in these plants of steroidal derivatives of pregnanes, pregnenolone in particular. The Buxus alkaloids appear to be derived from 4,4,14a-trimethyl-9j3,19-cyclo-5a-pregnanes. 

An approach to the total synthesis of cycloxobuxine and cycloprotobuxine alkaloids has been attempted starting from lanosterol.32 The pregnane derivative (38a), prepared from lanosterol,33 was transformed into the lljS-nitrite ester (38b), which was irradiated in benzene solution containing iodine. After oxidation of the resulting iodide, the 11 -oxo-19-iodo-derivati ve was transformed, through an alumina column,into 1 l-oxo-9/ , 19-cyclo-derivative (39) (cycloxobuxine skeleton). Reduction of (39) with lithium aluminium hydride gave a mixture of the triol (40) and the diol (41), the latter being oxidized to the diketone (42). 

The general utility of this method is nicely illustrated by its iq>plication to the synthesis of the cyclo-hexenone (24), a key synthetic intermediate in the synthesis of several of the Amaryllidaceae alkaloids, in 51 % overall yield from (23) as a mixture (1.5 1) of diastereomers (Scheme 8). 

Reactions of A -3-alkenyl nitrones are less stereoselective, and different stereoisomers of the same regioisomeric product are obtained101 102. In a synthesis of the alkaloid lasubine II, the thermal cycloaddition of the nitrone 1 gave an 83 10 7 mixture of bridged l-aza-7-oxabi-cyclo[2.2.1]heptanes, the major isomer possessing the correct stereochemistry for conversion into the natural product101. 

A review of the Buxus alkaloids with the 9/3,19-cyclo-14a-methyl-5a-pregnane skeleton has been published/ Pseudocyclobuxine D (67), the 3-epimer of cyclobuxine D, was isolated from Buxus sempervirens Structural assignment was achieved by i.r., n.m.r., and m.s. studies. Buxtauine, cyclomicrobuxine, cyclobuxine D, cycloprotobuxine C, and Na-benzoylcycloxobuxidine F have been isolated from the leaves of Buxus hyrcana Pojark. ... 

---