Julandine

Quinolizidine synthesis via intramolecular immonium ion based Diels-Alder reactions total synthesis of ( )-lupinine, ( )-epilupinine, ( )-criptopleurine and ( )-julandine [97]... 

Silicon (iv) chloride is an effective Lewis acid in the cyclization and subsequent dehydration steps of Herbert s synthesis of julandine and of cryptopleurine (cf. Vol. 10, p. 72).27 An early cryptopleurine synthesis has been improved.28... 

Returning to phenol ether-phenol ether coupling, synthetic septicine (59) gave ( )-tylophorine (60) on treatment with thallium trifluoroacetate, and the same reagent converted synthetic julandine (61) to ( )-cryptopleurine (62 69%). In another synthesis of tylophorine the lactam (63) was transformed with va-... 

Silicon(IV) chloride, SiCl4. Mol. wt. 169.90, b.p. 57.6°. Supplier Alfa. Silicon(IV) chloride is the most effective Lewis acid catalyst for dehydrative cyclization of the enamino ketone 1 to julandine (2). TiCI4 is almost as effective. Other Lewis acids are markedly less effective.1... 

The only enantioselective synthesis of julandine to date is due to Kibayashi and co-workers (593). Lewis acid-catalyzed condenseition between silyl enol ether 901 and the acyliminium ion formed from the proline-derived lactam 902 was highly diastereoselective (>99% de), giving a 76% yield of the piperidin-2-one 903 (Scheme... 

The pandemic nettle family, Urticaceae, was hardly known as a source of alkaloids until the isolation of the phenanthroquinolizidine base cryptopleurine (31) from two Boehmeria spp., together with certain others such as the seco-base, julandine (32), that appear to be biosynthetically related to it 47. The latter had not been recorded previously, but cryptopleurine was already known, having been obtained from a lauraceous plant referred to later apart from these examples, another genus of the Urticaceae, Cypholophus, produced cypholophine (33), a new type of imidazole alkaloid [48. ... 

Method 6. This synthesis is biomimetic (52), and the product of the first reaction, 33, occurs naturally along with oyptopleurine (18) in Boehmeria platyphylla and B. cylindrica (26,27). The penultimate stage is the alkaloid julandine (24), which also occurs in these two plants (26,27). The synthesis can be modified (52) to afford tylophorine (13) through the secophenanthro-indolizidine alkaloid septidne (30) (27,33,56). 

Cryptopleurine (24) and julandine (25) are phenanthroquinoUzidine alkaloids. Together with phenanthroindolizidine alkaloids, they are constituted by over 70 compounds. These alkaloids are commonly isolated from plants of Asclepiadaceae and Moraceae famihes [109,110]. They have exhibited similar biological activities, which include antiviral, antifungal, cytotoxic, and vesicant [111]. 

Sydnes MO, Bezos A, Bums C, Kruszelnicki I, Parish CR, Su S, Rae AD, Willis AC, Banwell MG (2008) Synthesis and biological evaluation of some enantiomerically pure C8c-C15 monoseco analogues of the phenanthroquinolizidine-type alkaloids cryptopleurine and julandine. Aust J Chem 61(7) 506-520. doi 10.1071/ch08190... 

The key step in the synthesis of julandine (68) is executed by treatment of an ethanol-water (1/1) solution of the diaryl amine hydrochloride 66 with formalin at 110°C in a sealed tube for 23 h. A single diastereomer, 67, is obtained in 60% yield and converted to julandine by an acid-catalyzed double-bond isomerization ... 

The higher reaction temperature is required in the imino Diels-Alder reaction leading to cryptopleurine, relative to julandine, since lower reaction temperatures give rise to numerous uncharacterized by-products. This is not surprising since effecting the [4+2] cycloaddition to produce cryptopleurine involves disruption of the aromatic phenanthrene unit followed by isomerization in situ to regain aromaticity. 

Grieco s synthesis of cryptopleurine 70 and julandine 68 (see end of section 2.3.1), via an intramolecular imino Diels-Alder reaction for construction of the quinolizidine nucleus, failed in the case of the related indolizidine alkaloid, tylophorine [38]. Submitting phenanthryl amine 113 to the identical aza Diels-Alder conditions used for cryptopleurine only yields by-products (114), as a result of a Clarke-Eschweiler type of cyclization. No tylophorine is detected under these conditions ... 

Figure 30 Structures of representative phenanthroindolizidine and phenanthroquino-lizidine alkaloids and seco analogs. The structures shown are those of the (S)- +)-enan-tiomers. Alkaloids septicine (1272) julandine (1273) tylophorine (1274) antofine (1275) cryptopleurine (1276) hispidine (1277).

Figure 31 Analogs of septidne and julandine (—)-secoantofine (1278) (—)-phylloste-mine (1281) (+)-tylophovatine A (1282) (+)-tylophovatine B (1283) tyloindicine F (1285) tyloindicine I (1286). The conventional numbering system for phenanthroindo-lizidine alkaloids is shown in structure 1280, and the same system is used for the seco analogs.

A bis(desmethyl) analog of julandine (1273) has been isolated from whole-plant extracts of Boehmeria siamensis Craib (Urticaceae), which is native to China, Laos, Vietnam, and Thailand.This brings the number of known secophenanthroquinolizidine alkaloids to three. Structure 1284 was assigned to the new but unnamed alkaloid after appftcation of the customary complement of spectroscopic techniques. However, its optical rotation was not reported, and the absolute configuration remains unknown. 

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