Diterpenes shifts 332

In the course of dolastane synthesis (the dolastanes are a group of marine diterpenes) interesting rearrangements catalyzed by Lewis acids were found. Treatment of the trienone 293 with excess (1.5 eq) ethylaluminum dichloride at low temperatures (—5°C, 48 h) gave the tetracyclic enone 295 in 53% yield while the tricyclic dienone 296 (50%) was formed at room temperature (equation 102)156. It was assumed that both products can be derived from the common zwitterion 294 which undergoes intramolecular alkylation at low temperatures (path a) whereas an alkyl shift takes place at elevated temperatures (path b), followed by a 1,2-hydride shift (equation 102). 

The configuration at C-13 of the diterpenes has been a problem for many years. NMR spectroscopy using chiral shift reagents has been suggested as a method to differentiate manool from 13-epi-manool [131]. Most of the diterpenes with a saturated side chain were present as mixtures of C-13 epimers. Small differences in chemical shifts in the H and l3C - NMR spectra did not allow assignement of the stereochemistry at C-13 [132]. 

Based on off-resonance decoupling, lanthanoid shift studies, spectral comparison with different analogues and decalin models, signal assignments of pimaradienes [550], kaura-noid diterpenes [551, 552], podocarpane derivatives [553] and labdanic diterpenes [554] could be achieved (Table 5.6). 

Table 5.6. Structures and 13C Chemical Shifts (c>c in ppm) of Selected Diterpenes. 

Measurements on these 13C-enriched compounds and the application of common assignment aids [73] led to the total signal identification of the following diterpenes the 13C shifts are outlined in Table 5.42. 

Table 5.42. 13C Chemical Shifts (<5C in ppm) of Diterpenes (Solvent CHC13) [1010],...

Volume 15 of this series features four important reviews of research on alkaloids. Chapter 1 by B. S. Joshi, S. W. Pelletier and S. K. Srivastava is the first comprehensive review of the carbon-13 and proton NMR shift assignments and physical constants of diterpene alkaloids and their derivatives. In addition to the catalogue of spectral and physical data, the chapter includes a table of the occurrences of these alkaloids in various plant species, tables containing molecular formulas versus calculated high-resolution mass values, and calculated high-resolution mass values versus the molecular formulas of diterpenoid alkaloids, as well as seven tables summarizing the carbon-13 chemical shifts of various functional groups in diterpenoid alkaloids. 

NMR chemical shifts and their assignment for 129 are shown with the structure below. The 1 0 NMR signals for the two methoxy groups in this diterpene apparently overlap at 1.6 ppm. The chemical shift of 1.6 ppm is viewed by the authors as consistent with values of methoxy groups in axial positions of simple cyclohexane ring systems and the assignment was made on that basis[l 10]. 

Some pairs of diastereomeric eitf-kaurane diterpenes were identified such as T2-T3, T4-T5, T8-T9, and T20-T21 [102], Crucial NMR shift values are listed in Tables 15 to 6 to help distinguish these diastereomers. In Table 4, H-l6 H NMR resonance signals of T2 and T3 are significantly different, because the anisotropic effect of the ent-kaurane C-ring made the H-16a shift downfield. It also caused the 13C NMR chemical shift of the 17-carboxylic acid to the upfield. On the other hand, the anisotropic effect of the carboxylic acid affected the resonance of C-15 (by about 5 ppm). The difference offers important evidence to distinguish this type of diastereomer. In the NOESY spectrum of T3, correlations between H-16a and H-13 or H-16a and H-14 proved its stereochemistry. The H-16 3 stereochemistry of T2 was reconfirmed by the NOE correlation between H-16(3 and H-l 1. 

Resembling methods used to elucidate the NOE correlation between H-17 and H-l 1 or H-17 and H-13 helped establish the stereochemistries of the 16,17-dihydroxy-enf-kaurane diterpenes. Relative to the 17-hydroxy-16a-ent- kaurane diterpenes, a 16a-hydroxy group results in the H NMR chemical shift of the 17-oxymethene more deshielded, but a 16 3-hydroxy group makes the 13C NMR shift of C-17 more deshielded. Diagnostic carbon signals of C-13 and C-16, especially C-13, are also key points to identify this type of diastereomer (see Table 17). Similar results (Table 18) were observed from the NMR data measured in different solvents. 

Standard analysis of spectroscopic data provided the structures of the xenicane diterpenes 107, 108 and 112 - 114 while the structure and stereochemistry of 106 were established via X-ray crystallography. The diacetoxypentose moiety in 110 and 111 was assigned as diacetoxyarabinose from 13C chemical shift data and coupling constant analysis. The total synthesis of 109 - 111 by Nicolaou et al. established that the ring junction stereochemistry for all three compounds was identical with that of eleutherobin (115) [100]. The structural similarity of these four compounds to the valdivones (101 - 105) is clearly evident. The total synthesis of 110 and 111 also confirmed the expected D-... 

The viscidanes exhibit an antipodal configuration at C7 compared to the bisabolane, serrulatane and decipiane diterpenes. This difference may reflect the involvement of a 3/ ,6 -acyclic precursor (211), or 3S,6E-, which cyclizes to the lS,7/ -intermediate (212) (Scheme 51). A 1,2-hydride shift with displacement of X would generate the tertiary carbocation (213) which could alkylate the Re-facc of CIO. The spiro-ring system produced (214) contains the 1,4-trans-disubstitution on the cyclopentane ring observed for the viscidane nucleus. A 1,5-hydride shift of the quasi-a ial allylic hydrogen in 214 and allylic rearrangement, with net yn-addition of water, completes the elaboration of the nucleus. Circumstantial support for the last step can be enlisted... 

In Teucrium diterpenoids C-6 position is also very important. Almost all of the neo-clerodane diterpenes have an oxygen function at that location, either as a hydroxyl, acetyl or a ketone, and sometimes as an ether function. In somecases, C-6 hydroxyl group forms a lactone with C-18 methylene group as in compounds 7, 14, 16. The hydroxyl or the acetyl groups could possess a or P stereochemistry. When the literature is studied, there are some discrepancies for the chemical shifts of the C-6 proton, either a or 3, it appears in the lowfield or highfield, as observed in compounds 77 and 78. 

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