Fig 1.
The synthetic pathway for preparation of 4,5-dihydroxy-3,6-dihydro-1,2-oxazines 11(R1,X,R2) and dihydroxy ɤ-lactones 8(R1,X).
Reagents and conditions: i) HOBt, DIC, DMF/DCM, rt, o.n.; ii) NH2OH·HCl, pyridine, 75°C, o.n. (for X = C-NO2), DMSO, DBU, 80°C, 20 h (for X = N); iii) TBAPI, sorbic acid, DCM, rt, 3 h; iv) OsO4, NMMO, DCM, rt, o.n.; v) Mo(CO)6, H2O, DMF, 100°C, 1 h; vi) TFA/DCM (1:1), rt, 1 hr; vii) amine, DMAP, HOBt, DIC, DMF/DCM, rt.
Fig 2.
Summary of the final lactones 8(R1,X).
[a] Purity was determined from LC traces with use of PDA detector; [b] Overall yield after the HPLC purification.
Fig 3.
Amines used for synthesis of carboxamides 9(R1,X, R2).
Fig 4.
Summary of the final oxazines 11(R1,X,R2).
[a] Purity was determined from LC traces with use of PDA detector; [b] Overall yield after the HPLC purification.
Fig 5.
Summary of the final oxazines 12(R1,X,R2).
[a] Purity was determined from LC traces with use of PDA detector; [b] Overall yield after the HPLC purification.
Fig 6.
Stereoselective formation of lactone 8(R1,X) demonstrated on one enantiomer of oxazine 5(R1,X).
Fig 7.
The ROESY experiment for derivative 8(1,1) with spatial interaction between HA and HB.
Fig 8.
Structures of the chiral selectors present on the amylose-derived CSPs.
Table 1.
The results of chiral HPLC separation of oxazines 11(R1,X,R2) and 12(R1,X,R2) and lactones 8(R1,X).[a]
Fig 9.
Examples of HPLC chromatograms of pure and crude oxazines 11(R1,X,R2) and 12(R1,X,R2).
a) 12(1,1,3) pure compound; b) 12(1,1,3) crude mixture; c) 12(4,1,1) pure compound (no chiral separation); d) 12(4,1,1) crude mixture (no chiral separation); e) 11(1,1,3) pure compound; f) 11(1,1,3) crude mixture.
Table 2.
The results of chiral SFC separation of oxazines 11(R1,X,R2) and 12(R1,X,R2) and lactones 8(R1,X).[a]
Fig 10.
Example of SFC chromatograms of pure and crude mixtures of oxazines 11(R1,X,R2) and 12(R1,X,R2).
a) 12(1,1,3) pure compound; b) 12(1,1,3) crude mixture; c) 12(4,1,1) pure compound; d) 12(4,1,1) crude mixture; e) 11(1,1,3) pure compound; f) 11(1,1,3) crude mixture.
Fig 11.
Comparison of HPLC (a) and SFC (b) method for analysis of lactone 8(1,2).