Section I of the thesis deals with the enantiospecific total synthesis of phomopsolide
B. Phomopsolide B was isolated from a strain of Phomopsis Oblonga. Enantiospecific total
synthesis of phomopsolide B was accomplished in 13 overall yield in 12 linear steps using (S)-lactic acid and L-tartaric acid as chiral pool precursors. Present approach involves the efficient use of -keto phosphonate derived from commercially available (S)-ethyl lactate.
Horner-Wadsworth-Emmons reaction and Still-Gennari olefination were employed as key
reactions in the synthesis (scheme 1).
Scheme 1: Total synthesis of phomopsolide B.
[This work has been published: Prasad, K. R.; Gutala, P. Tetrahedron 2012, 68, 7489-7493.]
Section II of the thesis describes the total synthesis of macrosphelides A and E which
are isolated from a culture broth of Microsphaeropsis sp. FO-5050 and from the strain Periconia byssoides. Total synthesis of macrosphelides A and E was accomplished in 19 overall yield from commercially available (S)-ethyl lactate. Horner-Wadsworth-Emmons reaction and Yamaguchi lactonization were employed as key reactions for the total synthesis of macrosphelides A and E (scheme 2).
Scheme 2: Total synthesis of macrosphelides A and E.
[This work has been published: Prasad, K. R.; Gutala, P. Tetrahedron 2011, 67, 4514-4520.]
Section III of the thesis deals with total synthesis and determination of absolute
configuration of synargentolide B 1. Synargentolide B 1 is a 5,6-dihydro--pyrone containing natural product and was isolated from Syncolostemon Argenteus by Rivett et al. in 1998 (fig 1). The relative stereochemistry at C-6, C-6′ positions in synargentolide B 1 was assigned to be R, S respectively based on the positive cotton effect in the CD spectrum.
Threo stereochemistry was proposed for the C1′-C2′ diol unit in synargentolide B 1 based on the NMR studies. The stereochemistry at C-5 could not be assigned, hence the structure of
synargentolide B 1 was tentatively proposed as 6R-[5,6S-(diacetyloxy)-1,2-(dihydroxy)-3Eheptenyl]-5,6-dihydro-2H-pyran-2-one (fig. 1).
Figure 1: Putative structure of synargentolide B 1.
Based on the tentative stereochemistry at the C-6, C-6′ positions proposed by Rivett
et al. and taking into consideration the threo relationship for the C-1′-C-2′ diol unit, it is anticipated that the structure of synargentolide B 1 could be one of the four possible diastereomers 1a-1d (fig 2).
Figure 2: Possible diastereomers of synargentolide B (1a-d).
Incidentally, one of the diastereomers 6R-[5R,6S-(diacetyloxy)-1S,2R-(dihydroxy)-
3E-heptenyl]-5,6-dihydro-2H-pyran-2-one 1d was a reported natural product isolated in
1990 from Hyptis oblangifolia by Pereda-Miranda, R. et al. along with its corresponding diacetylated product 2 (fig 3).
Fig. 3: Natural products isolated from Hyptis oblangifolia by Pereda-Miranda, R. et al.
Total synthesis and determination of absolute configuration of synargentolide B 1
were accomplished by synthesizing four possible diastereomers of the natural product (1a-1d) and by comparison of the spectral data of all synthesized diastereomers with that of reported for the natural product. Wittig-Horner reaction of -keto phosphonate derived from
(S)-lactic acid and ring closing metathesis reaction were employed as key reactions in the total synthesis of synargentolide B 1 (scheme 3 and 4).
Scheme 3: Total synthesis of possible diastereomers of synargentolide B (1a, 1b).
Scheme 4: Total synthesis of possible diastereomers of synargentolide B (1c, 1d).
[This work has been published: Prasad, K. R.; Gutala, P. J. Org. Chem. (in press)].
It was found that spectral data of 1a, 1b, 1c were not in agreement with that reported
for synargentolide B 1. However spectral data of 1d was in complete agreement with the data reported for synargentolide B 1. Spectral data of 1d was also in complete agreement with the data reported for the natural product isolated by Pereda-Miranda, R. et al.
Since the absolute stereochemistry of tetraacetate 2 is identical to the absolute
stereochemistry of 1d, we wanted to confirm the integrity of the diol 1d by synthesizing the corresponding acetate 2 which was also a natural product isolated by Pereda-Miranda et al.
1H NMR data of the synthesized tetraacetate 2 was in agreement with that reported for the isolated tetraacetate, while discrepancies were observed in the 13C NMR spectral data.
To clear the uncertainty, X-ray crystal structure analysis of the tetraacetate 2 was
performed. It was comprehensively proved that the structure of synthesized tetraacetate 2 was indeed same as the putative structure proposed for the isolated tetraacetate by Pereda-Miranda et al. The crystal structure analysis also confirmed the absolute stereochemistry of
the tetraacetate 2 and 1d (synargentolide B 1).
(For structural formula pl refer the abstract pdf file)
| Identifer | oai:union.ndltd.org:IISc/oai:etd.iisc.ernet.in:2005/3302 |
| Date | January 2013 |
| Creators | Gutala, Phaneendra |
| Contributors | Prasad, Kavirayani R |
| Source Sets | India Institute of Science |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | G25664 |
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