4- Hydroxy pipecolates

Though (25,47 )-4-hydroxy pipecolic acid 17 is a natural product it cannot be obtained in sufficient quantity from nature. A chiral pool synthesis from aspartic acid 19 is known involving... 

Even unactivated double bonds will cyclise onto reactive iminium salts as this synthesis of cis-4-hydroxy pipecolic acid 116 R = H shows. This is like a Prins reaction but involves an iminium ion instead of an aldehyde.18... 

The naturally occurring cis-5-hydroxy-L-pipecolic acid 40 was prepared from l-G1u in a stereospecific multistep reaction (88TL2231). Protected l-Glu was transformed into A -hydroxycycloornithine 41 in seven steps (94JOC929). 

Several methods were described for the preparation of pipecolic acid (hexahydropyridine-2-carboxylic acid) from Lys [57ZPC(308)179 59CCC2318 75BCJ1341 81JCS(P1)1769 82S163 83CC1169]. In a similar manner, 4-hydroxypipecolic acid was prepared from 5-hydroxy-L-Lys (65JA2030). 

Amino acids undergo similar nitrosation reactions to yield hydroxy acids or lactones. Diamino acids tend to yield cyclic imino acids, so that ornithine and lysine give rise to proline and pipecolic acid, respectively. 

The authors reported the chiral separation of proline and thereonine amino acid up to 20 and 6g, respectively, in a single run. Micropreparative resolution of lecucine was presented. The resolution was discussed with respect to the degree of sorbent saturation with copper(II), elution rate, eluent concentration, temperature, and column loading condition [16]. Weinstein [74] reported the micropreparative separation of alkylated amino acids on a Chiral ProCu column. In another article, a preparative chiral resolution of 3-methylene-7-benzylidene-bicyclo[3.3.1]nonane was achieved on 7.5% silver(I)-d-camphor- 10-sulfonate CSP [75]. Later, Shieh et al. [71] used L-proline-loaded silica gel for the chiral resolution of (ft,5 )-phcnylcthanolaminc as the Schiff base of 2-hydroxy-4-methoxyacetophenone. Gris et al. [76] presented the preparative separations of amino acids on Chirosolve L-proline and Chirosolve L-pipecolic acid CSPs. 

The total synthesis by the Ireland group was accomplished via Michael addition of the C8-C20 segment to the C21-C34 segment having a pipecolic ester moiety, and macrolactonization (Fig. 5). Their synthetic feature is that the C21-C24 a -allyl P-hydroxy ketone system is masked as 6,6-spiroketal during the synthesis and the labile a,p-diketoamide hemlketal system is prepared by oxidation of a masked enediol at a late stage. 

Conversion of piperidin-2-one to the cjco-cyclic enaminone by the Tebbe reaction allows the synthesis of the pipecolic acid derivative <97TA1115>. Enzymatic resolution of 3-hydroxy-... 

HyPic, hydroxy-3-picolinic acid 4-oxo-LPip, 4-oxo-L-pipecolic acid. 

L-PIpecolic acid piperidine-2-carboxylic acid, a nonproteogenic amino acid. It is formed from L-ly-sine, either by a-deamination followed by cyclization and reduction, or as a normal intermediate in the degradation of lysine to a-aminoadipic acid. The 4- and 5-hydroxy derivatives of L-P.a. are found especially in mimosas and palms. 

Hydroxy lysine, dehy d rolysino-norleucine. desmosine, pipecolic acid, mimosine. piperidine and quinolizidine alkaloids... 

This assumption, however, is not correct and there is substantial evidence that the a-amino group of lysine is removed by some still unknown reaction. Thus, Rothstein and Miller (148) demonstrated that DL-lysine-c-N was converted to pipecolic acid in the rat with the retention of much of the Still more direct CAddence is the isolation of a-hydroxy-e-amino-caproic acid from cultures of Neurospora grown with L-lysine-l-C (148). 

D-glucuronolactone to synthesize the epimeric 5-azido-sugars (32) and hence hydroxy-amino-acids which are proline or pipecolic acid derivatives, e.g., (33)-(35). (See also Chapter 24). 

Example of multistep chemo-enzymatic synthesis of pipecolic acid derivatives (60) and homoiminocyclitols (61) by two consecutive enzymatic aldol addition reactions (a) i-serine hydroxy-methyltransferase from Streptococcus thermophilus (lSHMTj ) (b) Cbz-OSu CHjCN/aqueous HCI (c) Cbz-OSu MeOH/SO CIj CaCI, NaBH, EtOH/THF CHjCN/aqueous HCI (d) o-threonine aldolase from Achromobacterxylosoxidans (oThrA j (e) FucA F131A (f) RhuA wild-type (g) acid phosphatase from potato type II and (h) H Pd/C. 

---