Z-Sparteine

At least seven other bases have been mentioned as present in the mother liquors from the manufacture of Z-sparteine sulphate. Valeur found two, sarothamnine and genisteine, of which Winterfeld and Nitzsche have confirmed genisteine and have themselves added four more, two, thought to be structural and two, optical isomerides of sparteine, with a fifth substance of higher boiling point. 

Since lupin seeds are used in some areas in cattle feeding, it is of practical as well as theoretical interest to determine the stage at which the seeds will be rich in the alkaloidal material responsible for toxicity. It has also been important to devise methods for the removal of alkaloids from the seeds so that the detoxified or debittered material can still be used as feed (111). Extraction procedures which accent the recovery of non-alkaloidal material have less interest to the alkaloid chemist than those which provide for the isolation of the pure organic bases. Given below are typical examples of the extraction procedures employed for the isolation of the lupin alkaloids lupinine, cytisine, Z-sparteine, d-lupanine, and anagyrine. The methods selected are representative of those utilized for the isolation of the less abundant or well-known lupin alkaloids as well. These methods are also representative of the different quantities of materials which are handled. One of the methods was selected (for anagyrine) to indicate some of the complexities of separation when there are a number of alkaloids present in a plant, rather than only one main alkaloidal constituent. The techniques of fractional distillation of the bases, fractional crystallization of alkaloid salts, such as perchlorates and picrates, and extractions dependent upon differential solubility have been employed for the isolation of pure individual alkaloids from a mixture. 

In the light of the prediction of the number of isomers of XCI, it is of interest to survey those CuHgeNg stereoisomers which have been isolated or prepared. In addition to d- and Z-sparteine ([a]p 17° in ethanol), which together constitute one of the three racemates, a new isomer appears to have been formed by dehydrogenation of Z-sparteine followed by rehydrogenation. (The assumption is made that the basic... 

The resolution of synthetic di-sparteine was achieved by Leonard and Beyler (278, 279) by means of i- and d-jS-camphorsulfonic acid, and both optically active forms of sparteine were obtained. The free bases were not isolated but each enantiomorph was identified through the formation of two known derivatives. The derivatives used to identify Lsparteine were the d-jS-camphorsulfonate and the dipicrate. The former salt was characterized by melting point, mixed melting point with an authentic sample, and specific rotation. The latter salt was characterized by melting point and mixed melting point with authentic I-sparteine dipicrate. d-Sparteine i- 3-camphorsulfonate had a specific rotation equal and opposite to its enantiomorphic Z-sparteine d-/3-camphorsulfonate. Characterization of d-sparteine was accomplished by conversion of the camphor-sulfonate salt to the dipicrate and monoperchlorate, both of which were... 

Sophoridine forms monoacidic salts (aurichloride, m.p. 189-190° picrolonate, m.p. 226-228°) and contains a lactam group (101). The electrolytic reduction product, C16H26N2, had a higher Zevorotation than Z-sparteine, [ ]d — 37.1° (ethanol), and differed also from sparteine in that it formed a dfmethiodide (m.p. >260°) (99). This C16H26N2 base was also different from the isomeric compound obtained on electrolytic reduction of sophocarpine. 

Sparteine. As already stated Z-lupanine and Z-anagyrine both yield d-sparteine on reduction. This base was found in Sophora pachycarpa by Orekhov, who continues to use the name pachycarpine for it, and with Kabatschnik and Kefeli ( l has described experiments with oxypachycarpine, on the results of which he adopts for this substance formula (VIII with CH at 10 —> CO) which makes it identical with oxysparteine. from other plants (Nos. 1, 2, 4, 31, list, pp. 116-8). 

Although not of industrial importance, several asymmetric syntheses of (R)-pantolactone (9) have been developed. Stereoselective abstraction of the j Z-proton of the achiral 1,3-propanediol derivative (23) by j -butyUthium-(-)-sparteine, followed by carboxylation and hydrolysis, results in (R)-pantolactone in 80% yield and 95% ee (53). 

In 1931 Winterfeld and Kneuer, as a result of their observation that jS-lupinane can be obtained from lupanine, and the formation of 2-methyl-pyrrolidine by the oxidation of sparteine, combined these two features in a partial formula (II) for lupanine, which could be developed in various ways depending on the mode of attachment of the methylpyrrolidine residue. In view, however, of Ing s demonstration of the relationship of anagyrine, CJ5H20ON2, to Z-lupanine, CJ5H24ON2, and d-sparteine, C15H28N2, it was elearly neeessary to consider formul for lupanine derivable from the two alternati-ves, which Ing had proposed for anagyrine and which are shown below as (III) and (IV) with the formul for lupanine derived from them (V) by Ing and (VI) by Clemo and Raper. Sparteine would be represented by (V) or (VI) with the change CO CH2. 

Thus the product in such cases can exist as two pairs of enantiomers. In a di-astereoselective process, one of the two pairs is formed exclusively or predominantly as a racemic mixture. Many such examples have been reported. In many of these cases, both the enolate and substrate can exist as (Z) or (E) isomers. With enolates derived from ketones or carboxylic esters, (E) enolates gave the syn pair of enantiomers (p. 146), while (Z) enolates gave the anti pair. Addition of chiral additives to the reaction, such as proline derivatives, or (—)-sparteine lead to product formation with good-to-excellent asynunetric induction. Ultrasound has also been used to promote asymmetric Michael reactions. Intramolecular versions of Michael addition are well known. ... 

The asymmetric deprotonation can be advantageously coupled with intramolecular cyclocarbolithiations . (E)- and (Z)-6-phenylhex-5-enyl carbamates 55 are Hthiated by s-BuLi/(—)-sparteine adjacent to the carbamoyloxy group (equation 13). The intermediates... 

Contrary to Uthiated alkyl carbamates, which hold a pyramidalized sp -hybridized carb-anionic centre and thus generally react with electrophiles under retention of configuration (see Section n.B.l), lithiated ( )-allyl carbamates 310 have a high tendency for antarafa-cial reactions, which seem to be enforced by the bulky sparteine as the lithium ligand (equation 79). Fortunately, in these reactions, the Af,Af-diisopropylcarbamoyloxy group prefers the ewdo-position to lead to the a-product 311 (inversion) and to the y-product (Z)-312 [sometimes besides small amounts of (E)-ent-312)]. 

The stannylation of (25,3 )-2-(iV,Af-diisopropylcarbamoyloxy)-3-penten-2-yllithium-(—)-sparteine [( )-300b] takes place with complete y-regioselectivity, leading to an E/Z-diastereomeric mixture of (R,Z)- and (5, )-315 (equation 82) . 

Since carbohthiations usually proceed as syn additions, 458 is expected to be formed first. Due to the configurationally labile benzylic centre it epimerizes to the trani-substitu-ted chelate complex epi-45S. The substitution of epi-458 is assumed to occur with inversion at the benzylic centre. Sterically more demanding reagents (t-BuLi) or the well-stabilized benzyllithium do not add. The reaction works with the same efficiency when other complexing cinnamyl derivatives, such as ethers and primary, secondary, or tertiary amines, are used as substrates . A substoichiometric amount (5 mol%) of (—)-sparteine (11) serves equally well. The appropriate (Z)-cinnamyl derivatives give rise to ewf-459, since the opposite enantiotopic face of the double bond is attacked . 

W-Substituted 2,4-alkadien-l-ols such as 474 add the alkyllithium/(—)-sparteine complex preferentially to the 2-position to form via the alkoxide the corresponding allyllithium intermediates 475 . Protic workup leads to a mixture of ii/Z-alkenols 476 and 477 on catalytic hydrogenation the -branched alcohols 478 are isolated (equation 130). 

Epiaphylline was isolated ftomLupinus hartwegii (146-147). The mass spectrum of this alkaloid is characterized by peaks at m/z 248 (70), 247 (46), 220 (45), 137 (47), 136 (100), 97 (53), and 96 (45%) that are tyical for sparteine alkaloids. The peak at m/z 220 originates from the splitting of a carbonyl group. Epiaphylline (110), in contrast to aphylline (108), did not react under mild catalytic hydrogenation conditions, but under harsher conditions epiaphylline (110) converted to 3-isosparteine (14) (Scheme 14). This established the presence of a carbonyl group at C-10. 

Beak and co-workers have also produced the key alcohol intermediate 74 by the sparteine-mediated lithiation and conjugate addition of allylamines to nitroalkenes to give Z-enecarbamates in good yields with high enantio- and diastereoselectivty (Scheme 16). Thus treatment of the allylamine 87 with n-BuLi in the presence of (-)-sparteine followed by conjugate addition to nitroalkene 88 gave the desired enecarbamate 89 in... 

As shown in Scheme 33, the synthesis of the C1-C7 amide 160 began with a Hoppe crotyltitanation reaction between the aldehyde 17 and the (R)-crotyltitanium 163, prepared in situ (crotyl diisopropylcarbamate with sBuLi/(-)-sparteine/ Ti(0/Pr)4), to give O-enecarbamate 164 (>30 ldr) [166-169], Ozonolysis and HWE chain extension was followed by an Evans-Prunet 1,4-addition to install the C5-stereocentre to complete 160 [103], The synthesis of the C8-C14 subunit 161 started with an elegant installation of the C13-C14 (Z)-olefin. Deprotonation of the dihydrofuran 165, available in three steps from bromo alcohol 166, with fBuLi and transmetallation with Me2CuLi LiCN, and subsequent 1,2-cuprate transfer gave the... 

Wink, M. 1987. Site of lupanine and sparteine biosynthesis in intact plants and in vitro organ cultures. Z. Naturforsch. 42, 868-872... 

Beak used this method in a synthesis of (-)-paroxetine 97 (Paxil or Seroxat), a selective serotonin reuptake inhibitor.9 Lithiation of 92 with n-BuLi-(-)-sparteine and addition of the product 93 to the nitroalkene 94 yields the protected Z-enamine 95, as usual for reactions of lithiated allylamides, in >94% ee. Hydrolysis and reduction of the product, followed by mesylation and cyclisation gave the fnms-substituted piperidine 96. Displacement of the hydroxyl group by sesamol yielded (-)-paroxetine 97. 

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