Proline derivatives, synthesis

Cheong, P. H.-Y Houk, K. N. Origins and predictions of stereoselectivity in intramolecular aldol reactions catalyzed by proline derivatives, Synthesis 2005, 1533-1537. 

But it can be assumed that kororamide A is derived from the combinations of brominated tryptophan derived metabolite and proline derivative. Synthesis of kororamide A (141) is not reported in literature. 

Proline derivs., synthesis, asym., with - 21, 835 suppl. 26... 

Reciystallizations of the Gringard addition product as the toluenesulfonate salt were less detailed, providing students the opportunity to optimize their purification procedures. Figure 56.3 shows the synthesis of the starting L-proline derivative used in the laboratoiy. 

The key step in the total synthesis of (—)-epilupinine 253 involved the ring expansion of a proline-derived spirocyclic ammonium ylide to give 252 through a [1,2] Stevens rearrangement, as shown in Scheme 51 <1997T16565>. 

A very interesting organocatalyzed one-pot Michael addition/aldol condensation/Darzens condensation has been reported for the asymmetric synthesis of epoxy-ketones <06JA5475>. An initial asymmetric Michael condensation between 16 and 17 is catalyzed by proline derivative 18. Intermediate 19 then undergoes an aldol condensation followed by a stereoselective Darzens condensation to provide epoxy-ketone 20 in moderate yield and with surprisingly good enantiomeric excess. 

Gais and co-workers recently reported the preparation and use of chiral sulfoximine-substituted allyltitanium(iv) complexes of type 78 for the asymmetric synthesis of 3-substituted unsaturated proline derivatives 79 (Scheme 31).108... 

Proline has been often used in reactions with aldehydes to form 1-oxo perhydropyrrolo[l,2-f]oxazole structures <1998J(P1)3777, 2004PNA5839>. These compounds were used for the asymmetric synthesis of proline derivatives which are present in natural products or analogs (Scheme 49) <2005T10018, 2005TA2075, 2006JOC97>. 

The addition of a titanium homoenolate 115 to a proline derivative 114 proved to be a feasible approach for the formal synthesis of pumiliotoxin 251D. The addition proceeded with high stereoselectivity (Scheme 30) <1999JOC1410>. 

In the search of new methodologies for the asymmetric synthesis of nonproteinogenic amino acids, 8-methyl-4,8a-diphenyltetrahydro-17/-pyrrolo[2.1 -r l, 4 oxazinc-l, 6(7//)-dionc 62, obtained as described in Scheme 24 (Section 11.11.7.3), was selectively reduced at the lactam carbonyl with BH3 and further opened by hydrogenolysis to give syn-disubstituted proline derivative 64 in 95% yield <1997SL935> (Scheme 6). It is noteworthy that hydrogenolysis did not affect the benzylic position of bicyclic compound 63. 

Scheme 49 Parallel synthesis for N-a-substituted proline derivatives.

The Corey synthesis began with an asymmetric Diels-Alder reaction between butadiene and 2,2,2-trifluoroethyl acrylate in the presence of the 5-proline-derived catalyst ent-59 to form the adduct ent-69 in excellent yield (97%) and with >97% ee (Scheme 7.10). Ammonolysis of 60 produced amide 61 quantitatively, which underwent iodolacta-mization using the Knapp protocol to generate lactam 62. A-Acylation of 62 with... 

Murahashi and co-workers (49) extensively studied the synthesis of nitrones such as 29 by a decarboxylative oxidation of proline derivatives (Scheme 12.12). However, these nitrones were primarily used in nucleophilic addition reactions rather than 1,3-dipolar cycloadditions. Others have synthesized cyclic nitrones 30 and 31 having a chiral center adjacent to the nitrogen atom (50,51). Saito and co-workers (51) applied nitrone 31 in reactions with fumaric and maleic acid... 

Stereoselective addition of hydrogen to a C=C double bond of an (S)-proline derivation was applied in the total synthesis of gephyrotoxin, a biologically active alkaloid 87). Optically active pyrrolizidine bases have been synthesized by Robins and Sakdarat88) from chiral hydroxyproline derivatives by hydrogenation (ds > 60 %). 

In the asymmetric synthesis of 4,4-disubstituted cyclohexenones of the type (132) it was possible to raise the optical yield to a maximum of 54 % by varying the structures of the carbonyl compounds 150) and of the proline derivatives (131)151). 

Enders and Lotter174) developed an asymmetric synthesis of a-hydroxyketones and vicinal diols using the (S)-proline derivative (S)-l-formyl-2-methoxymethyl-pyrrolidine as chiral auxiliary. However, the a-hydroxyketones and vicinal diols, respectively, were only obtained with low stereoselectivity. 

When (2S)-1-(1-cyclohexene-l-yl)-2-(methoxymethyl)pyrrolidine (206), enamine from cyclohexanone, and (S)-proline-derived (2S)-(methoxymethyl)pyrrolidine is added to the Knoevenagel condensation products (207), mainly one of the possible four diastereomers is formed. The diastereomeric purity was found to be excellent (d.s. > 90%) 203). The stereochemical course of this highly effective asymmetric synthesis allowed the synthesis of the optically active target molecules (208). A possible mechanism discussed by Blarer and Seebach 203). 

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

Thiruvazhi et al. [112] have shown interest in the area of (3-tum mimetics and the synthetic application of d- and L-proline for asymmetric synthesis of proline-derived spiro-(3-lactams. It has been shown that the asymmetric Staudinger reaction of optically active acid chloride of d- and L-proline with achiral imines is impossible due to the loss of stereochemistry at C-2. The authors have developed a strategy in which a chiral group at C-4 of the acid chloride of proline directs the stereoselectivity of the reaction and is sacrificed later to obtain optically active spiro-(3-lactams (Scheme 38). 

Scheme 38 Asymmetric synthesis of proline-derived spiro-fS-lactams...

In 2008 Resmini et al. [76] presented their work on the synthesis of novel molecularly imprinted nanogels with Aldolase type I activity in the cross-aldol reaction between 4-nitrobenzaldehyde and acetone. A polymerisable proline derivative was used as the functional monomer to mimic the enamine-based mechanism of aldolase type I enzymes. A 1,3-diketone template, used to create the cavity, was... 

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