N-phosphoryl　amino　acids　(PAAs)　are　important　species　in　the　origin　of　life　that　self-catalyze　and　self-assemble　into　polypeptides　and　polynucleotides　under　mild　conditions.　Both　experimental　and　theoretical　studies　have　shown　that　a　penta-coordinated　phosphorus　intermolecular　mixed　carboxylic-phosphoric　anhydride　(IMCPA)　is　formed　as　the　common　intermediate　in　these　reactions.　In　this　work,　the　mechanism　for　the　formation　of　stereoisomeric　IMCPAs　from　PAAs　is　investigated　using　density　functional　theory　(DFT)　calculations　at　the　B3LYP/6-311+G(d,p)　theoretical　level.　The　molecular　structures　of　the　cis-　and　the　trans-IMCPAs,　as　well　as　the　transition　states　of　the　two　stereochemical　reaction　pathways,　were　characterized　in　detail.　The　results　showed　that　the　hydroxyl　groups　of　PAAs　were　situated　in　favorable　positions　for　attacking　the　phosphorus　atom　from　two　sides　of　the　phosphoryl　group,　resulting　in　the　formation　of　the　cis-IMCPA　and　the　trans-IMCPA,　respectively.　The　trans-isomers　were　predicted　to　be　more　likely　to　undergo　a　further　reaction　involving　an　ester　exchange　on　the　phosphorus　than　the　cis-isomers.　By　comparing　the　relative　energies　of　the　IMCPAs　and　the　activation　energies,　the　trans-IMCPAs　were　computed　to　be　more　stable　than　the　cis-IMCPAs,　but　the　energy　barriers　for　the　formation　of　the　trans-　and　the　cis-isomers　were　similar.　This　work　is　expected　to　shed　light　on　the　stereochemical　effect　involved　in　the　chemical　evolution　of　biomolecules.